Daniel Abbott, MD (PGY5), Department of Surgery

Education:

B.S., Washington State University, 1999
M.D., University of Washington School of Medicine, 2003

Research Interests:

Our laboratory investigates the interaction of tumor cells with their micro-environment.  Specifically, we are interested in alterations in tumor cell phenotype when the extra-cellular matrix composition is manipulated.  Additionally, we examine preferentially secreted proteins from both benign and malignant cells, identifying the role of secreted proteins in invasion, migration, proliferation and angiogenesis.

Publications:

Lynne-Marie Postovit, Daniel E. Abbott, Stacey L. Payne, William W. Wheaton, Naira V. Margaryan, Richard Sullivan, Matthias K. Jansen, Katalin Csiszar, Mary J.C. Hendrix, and Dawn A. Kirschmann. Hypoxia/reoxygenation: A dynamic regulator of lysyl oxidase-facilitated breast cancer migration,submitted to Cancer Research (Priority Report) February 2007.  (* denotes shared first-authorship)

Khalkhali-Ellis, Z., Margarian, NV, Bailey, C.M., Wheaton, W.W., Abbott, D.E. and Hendrix. M J.C. (2006). Mammary Epithelial Cell Specific Regulation of Lysosomal Targeting and Secretion of Cathepsin D by  Maspin. Mol. Biol. Cell. (submitted).

Daniel E. Abbott, Michael J. Liptay, Mediastinoscopy (book chapter), Adult Chest Surgery: Concepts and Procedures, McGraw-Hill Professional publishers, David J Sugarbaker editor, (in press).

Daniel Abbott, Amy L. Halverson, Jeffrey Wayne, John Kim, Mark Talamonti, and Gregory A. Dumanin, The ORAM Flap for Complex Pelvic Wound Reconstruction, submitted to Disease of the Colon and Rectum 1/07.

Daniel Abbott, Gregory A. Dumanian, Amy L. Halverson, Management of Laparotomy Wound Dehiscence, submitted to American Journal of Surgery, 2/07.

Bilimoria, KB, Abbott, DE, Wayne, J, DeRosa, D, How to Design a Pilot System for Tracking Adverse and Near-Miss Events in Surgical Patients, American College of Surgeons Web Site, (Residency Assist Page), 2004.

Manuscripts in Preparation

Lynne-Marie Postovit, Naira V. Margaryan, Elisabeth A. Seftor, Richard E.B. Seftor, William W. Wheaton, Daniel E. Abbott, Mary J.C. Hendrix, Human Embryonic Stem Cell Microenvironment Reverses the Plastic Phenotype of Tumor Cells, for submission to Cancer Research.

Edward D. Auyang, MD (PGY4) Department of Surgery

Education:

B.S., The Johns Hopkins University, Biomedical Engineering, Minor in Computer Science, 1997
M.S., University of Cincinnati, College of Medicine, Environmental/Occupational Health, 2000
M.D., The Ohio Sate University College of Medicine and Public Health, 2004

Research Interests:

Publications:

Auyang ED, Murayama K, Nagle A. Five-Year follow-up after laparoscopic Roux-en-Y gastric and partial ileal bypass for treatment of morbid obesity and uncontrolled hyperlipidemia. Obesity Surgery (2008) (In Press).

Auyang ED, Vaziri K, Volckmann E, Martin JA, Soper NJ, Hungness ES. NOTES: Cadaveric Rendezvous Hybrid Small Bowel Resection (with video). Surg Endosc (2008) (In press).

Bhattacharya A, Shukla R, Auyang ED, Dietrich KN, Bornschein R. “Effect of succimer chelation therapy on postural balance and gait outcomes in children with early exposure to environmental lead.”  Neurotoxicology (2007) 28:686-695.

BOOK CHAPTERS:

Auyang ED and Soper NJ. “Laparoscopic Cholecystectomy” in International Principles of Laparoscopic Surgery, Frezza EE ed., Cine-Med, (In Press).

ABSTRACTS and PRESENTATIONS:

Auyang ED, Koons A, Soper NJ, Kramer S, Hungness ES. “Early Systemic Cytokine Response of NOTES Compared to Traditional Surgery”. 3rd International Conference on Natural Orifice Translumenal Endoscopic Surgery, San Francisco, CA, July 10-12, 2008.

Auyang ED, Vaziri K, Martin JA, Hungness ES, Soper NJ. “Human NOTES Hybrid Transgastric Cholecystectomy.” Digestive Disease Week / SSAT Annual Conference, San Diego, CA, May 20, 2008.

Auyang ED, Vaziri K, Martin JA, Hungness ES, Soper NJ. “NOTES: Dissection of the Critical View of Safety During Transcolonic Cholecystectomy.” Digestive Disease Week / SSAT Annual Conference, San Diego, CA, May 21, 2008.

Vaziri K, Auyang ED, Soper NJ, Hungness ES. “Laparoscopic Celiac Artery Decompression.” Digestive Disease Week / SSAT Annual Conference, San Diego, CA, May 20, 2008.

Auyang ED, Vaziri K, Volckmann E, Martin JA, Soper NJ, Hungness ES. “NOTES: Cadaveric Rendezvous Hybrid Small Bowel Resection”, SAGES Annual Conference, Philadelphia, PA, April 11, 2008.

Auyang ED, Vaziri K, Martin JA, Hungness, ES, Soper NJ.  “Human NOTES Hybrid Transgastric Cholecystectomy” Northwestern University Feinberg School of Medicine 4th Annual Lewis Landsberg Research Day, Chicago, IL, March 19, 2008.

Auyang ED, Hungness, ES, Soper NJ.  “Human NOTES Hybrid Transgastric Cholecystectomy” Chicago Surgical Society: Scientific Presentations Chicago, IL, February 7, 2008.

Hobgood T, Kosicki G, Nockowitz R, Auyang E, Sullivan M, Powell D. “Optimizing Workplace Safety in Facial Plastic and Reconstructive Surgery: Identification and Management of the Unstable Patient.” American Academy of Facial Plastics and Reconstructive Surgery Annual
Conference. New York, NY, May 1-5, 2002.

NO PICTURE AVAILABLE

Karl Y. Bilimoria, MD (PGY5), Department of Surgery

Education:

B.S., Northwestern University, Molecular and Cell Biology, 1998
M.D., Indiana University School of Medicine, 2003

Research Interests:

Dr. Bilimoria is a general surgery resident who is currently a Clinical Scholar at the American College of Surgeons and obtaining a Masters in Clinical Investigation at Northwestern.  Dr. Bilimoria’s work focuses on improving the delivery of oncologic surgery in the United States, particularly at Community hospitals.  His research primarily concerns pancreatic cancer outcomes but also includes other gastrointestinal and endocrine malignancies.

Publications:

Heppner C, Bilimoria KY, Agarwal SK, et al. The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation. Oncogene 2001; 20(36):4917-25.

Bilimoria KY, Eagan RK, Rex DK. Colonoscopic identification of a foreign body causing an hepatic abscess. J Clin Gastroenterol 2003; 37(1):82-5.

Bilimoria KY, Pescovitz OH, DiMeglio LA. Autoimmune thyroid dysfunction in children with type 1 diabetes mellitus: screening guidelines based on a retrospective analysis. J Pediatr Endocrinol Metab 2003; 16(8):1111-7.

Bilimoria KY, Rothenberg JM. Prenatal diagnosis of a trisomy 7/maternal uniparental heterodisomy 7 mosaic fetus. Am J Med Genet A 2003; 118(1):60-3.

Bilimoria K, Sturgis C, Liptay M. Metastatic breast cancer and lung cancer within the same lymph node. Int J Surg Pathol 2007;15(2):169.

Bilimoria KY, Bentrem DJ, Ko CY, et al. Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database. Cancer 2007; 110(4):738-44.

Bilimoria KY, Bentrem DJ, Ko CY, et al. National failure to operate on early stage pancreatic cancer. Ann Surg 2007; 246(2):173-80.

Bilimoria KY, Bentrem DJ, Ko CY, et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 2007; 246(3):375-81; discussion 381-4.

Bilimoria KY, Bentrem DJ, Ko CY, et al. Multimodality therapy for pancreatic cancer in the U.S. : utilization, outcomes, and the effect of hospital volume. Cancer 2007; 110(6):1227-34.

Bilimoria KY, Bentrem DJ, Linn JG, et al. Utilization of total thyroidectomy for papillary thyroid cancer in the United States. Surgery 2007; 142(6):906-13.

Bilimoria KY, Bentrem DJ, Merkow RP, et al. Application of the Pancreatic Adenocarcinoma Staging System to Pancreatic Neuroendocrine Tumors. J Am Coll Surg 2007; 205(4):558-563.

Bilimoria KY, Bentrem DJ, Tomlinson JS, et al. Quality of pancreatic cancer care at Veterans Administration compared with non-Veterans Administration hospitals. Am J Surg 2007; 194(5):588-93.

Bilimoria KY, Cambic A, Hansen NM, Bethke KP. Evaluating the impact of preoperative breast magnetic resonance imaging on the surgical management of newly diagnosed breast cancers. Arch Surg 2007; 142(5):441-5; discussion 445-7.

Bilimoria KY, Stewart AK, Tomlinson JS, et al. Impact of Adjuvant Radiation on Survival: A Note of Caution When Using Cancer Registry Data to Evaluate Adjuvant Treatments. Ann Surg Oncol 2007.

Bilimoria KY, Tomlinson JS, Merkow RP, et al. Clinicopathologic features and treatment trends of pancreatic neuroendocrine tumors: analysis of 9,821 patients. J Gastrointest Surg 2007; 11(11):1460-9.

Blum MG, Bilimoria KY, Wayne JD, et al. Surgical considerations for the management and resection of esophageal gastrointestinal stromal tumors. Ann Thorac Surg 2007; 84(5):1717-23.

Kennedy T, Stewart AK, Bilimoria KY, et al. Treatment Trends and Factors Associated with Survival in T1aN0 and T1bN0 Breast Cancer Patients. Ann Surg Oncol 2007; 14(10):2918-27.

Bilimoria KY, Balch CM, Bentrem DJ, et al. Complete Lymph Node Dissection for Sentinel Node-Positive Melanoma: Assessment of Practice Patterns in the United States. Ann Surg Oncol 2008.

Bilimoria KY, Bentrem DJ, Ko CY, et al. Squamous Cell Carcinoma of the Anal Canal: Utilization and Outcomes of Recommended Treatment in the United States. Ann Surg Oncol 2008.

Bilimoria KY, Palis B, Stewart AK, et al. Impact of tumor location on nodal evaluation for colon cancer. Dis Colon Rectum 2008; 51(2):154-61.

Bilimoria KY, Stewart AK, Edge S, Ko CY. Lymph Node Examination Rate, Survival Rate, and Quality of Care in Colon Cancer. JAMA 2008; 299 (8):896-7.

Bilimoria KY, Stewart AK, Palis BE, et al. Adequacy and importance of lymph node evaluation for colon cancer in the elderly. J Am Coll Surg 2008; 206(2):247-54.

Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol 2008; 15(3):683-90.

Bilimoria KY, Talamonti MS, Tomlinson JS, et al. Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors: analysis of 3851 patients. Ann Surg 2008; 247(3):490-500.

Bilimoria KY, Winchester DP. The importance of worldwide Cancer Registration. J Surg Oncol 2008.

Lo DJ, Bilimoria KY, Pugh CM. Bowel complications after prolene hernia system (PHS) repair: a case report and review of the literature. Hernia 2008.

In press:

Karl Y. Bilimoria, Cord Sturgeon, David P. Winchester. Concern Regarding the Extent of Surgery for Papillary Thyroid Cancer Annals of Surgery 2008.
   
Karl Y. Bilimoria, Mark S. Talamonti, Jeffrey Wayne, James S. Tomlinson, Andrew K. Stewart, David P. Winchester, Clifford Y Ko, David J. Bentrem. Effect of Hospital Type and Volume on Nodal Evaluation for Gastric and Pancreatic Cancers. Archives of Surgery 2008.
   
Karl Y. Bilimoria, David J. Bentrem Joseph M. Feinglass, Mark S. Talamonti, Andrew K. Stewart, David P. Winchester, Clifford Y. Ko. Directing Surgical Quality Improvement Initiatives in the United States: Comparison of Perioperative Mortality and Long-Term. Survival for Cancer Surgery.  Journal of Clinical Oncology 2008.
   
Karl Y. Bilimoria, Charles M. Balch, David J. Bentrem, Mark Talamonti, Clifford Y. Ko, Julie R. Lange, David P. Winchester, Jeffrey D. Wayne. Complete Lymph Node Dissection for Sentinel Node-Positive Melanoma: Assessment of Practice Patterns in the United States. Annals of Surgical Oncology 2008.

Karl Y. Bilimoria, Thomas Kmiecik, Debra DaRosa, Richard H. Bell, Nathaniel J. Soper, Jeffrey D. Wayne. Development of an Online System to Assess Patterns of Adverse and Near-Miss Events. Archives of Surgery 2008.
   
Karl Y. Bilimoria, David J. Bentrem, Clifford Y. Ko, Mark S. Talamonti, Amy Halverson. Squamous Cell Carcinoma of the Anal Canal: Utilization and Outcomes of Recommended Treatment in the United States. Annals of Surgical Oncology 2008.

Karl Y. Bilimoria, David J. Bentrem, Heidi Nelson, Steven J. Stryker, Nathaniel J. Soper, Andrew K. Stewart, Thomas R. Russell, Clifford Y. Ko. Laparoscopic-Assisted Colectomy for Cancer: Utilization and Outcomes in the United States. Archives of Surgery 2008.

Karl Y. Bilimoria, Mark S. Talamonti, Stephen F. Sener, Malcolm M. Bilimoria, Andrew K. Stewart, David P. Winchester, Clifford Y. Ko, David J. Bentrem. Impact of Hospital Volume on Margin Status after Pancreaticoduodenectomy for Cancer. Journal of the American College of Surgeons 2008.   

Michael Burke, MD, (PGY4), Department of Medicine

Education:

B.S.,Villanova University, Comprehensive, 1999
M.D., Thomas Jefferson University, 2004

Research Interests:

During college and graduate school, I performed research in molecular and cellular biology.  In addition, I gained an appreciation for the intricacies and importance of research to the fields of biology and medicine.  During medical school, I again performed research in molecular biology, this time, molecular cardiology.  This experience though was different.  I was interacting with patients and subsequently performing research in the lab.  This is the essence of the newly evolving field of translational medicine: to be able to move from bench to bedside and back with the goal of more rapidly integrating the rapid advances in the basic sciences with clinical advances for our patients.  I plan on performing research in molecular cardiology with the ultimate goal of establishing a career in translational medicine.

Publications:

Burke MA, Hutter D, Reshamwala RP and Knepper JE. Cathepsin L plays an active role in involution of the mouse mammary gland. Dev Dyn. 2003;227:315-22.

Burke MA and Cotts WG. Interpretation of B-type natriuretic peptide in cardiac disease and other comorbid conditions.  Heart Fail Rev.  2007;
12:23-36.

Burke MA and Ardehali H. Mitochondrial ATP Binding Cassette Proteins. Transl Res. 2007; 150:73-80.

Burke MA, Mutharasan RK and Ardehali H.  The sulfonylurea receptor, an atypical ATP-binding cassette protein, and its regulation of the KATP channel.  Circ Res. 2008; 102:164-176.

Jessica F. Curley, MD, PhD (PGY6), Department of Pediatrics

Education:

B.S., University of Vermont, Chemistry, 1993
Ph.D., University of Chicago, Chemistry, 1999 
M.D., University of Chicago, 2002

Research Interests:

As an undergraduate, she researched synthesis and structures of diiridium compounds in the laboratory of Dr. Kazi Ahmed. With Dr. Joseph Piccirilli, she investigated the role of the metal ions in the 3'-5' xonuclease reaction of DNA Polymerase I from E. coli. From 2002-05, as a resident in Pediatrics at University of Chicago, she worked with Dr. Sally Radovic investigating the molecular basis for pituitary deficiency. In 2005, she joined the fellowship program in Pediatric Kidney Diseases at Children's Memorial Hospital in Chicago and began researching the role of stretch in TGF-beta induced extracellular matrix accumulation in human mesangial cells.

Publications:

Kolel-Veetil, M. K., Curley, J. F., Yadav,P. R., Ahmed, K. J.  The X-ray Structure and Substitution Reactions of the Amido Bridged IrII Dimer Ir2(I)2[?-NH(p-tolyl)]2(CO)4. Polyhedron  1994, 13, 919.

Curley, J. F., Joyce, C. M., and Piccirilli, J. A.  Functional Evidence That the 3’-5’ Exonuclease Domain of  Escherichia coli DNA Polymerase I Employs a Divalent Metal Ion in Leaving Group Stabilization.  J. Am. Chem. Soc. 1997, 119, 12691.

Liao, X., Anjaneyulu, P.S.R., Curley, J. F. Hsu, M.,  Piccirilli, J. A.  The Tetrahymena Ribozyme Cleaves a 5’-Methylene Phosphonate Monoester ~102 fold faster than a Normal Phosphate Diester:  Implications for Enzyme Catalysis of Phosphoryl Transfer Reactions. Biochemistry 2001, 40, 10911.

Sunit Das, MD, PhD (PGY5), Department of Neurological Surgery Education: B.A., University of Michigan, English Literature, 1995 M.A., Harvard University, Philosophy, 1996 M.D., Northwestern University, 2001 Ph.D.,  NINDS, NIH, 2003 Subspecialty Interest: Neuro-Oncology

Research Interests: As a medical student, I worked in the laboratory of Dr John Disterhoft, a neurophysiologist interested in the biology of associative learning and in the role of the hippocampus and cerebellum in adaptive memory.  His lab has utilized slice recording as well as ablation techniques to detail anatomical correlates of behavioral changes brought about during operant conditioning.  I designed and tested a paradigm using mystacial vibrissae stimulation in the rabbit as a mechanism for operant conditioning.  My work demonstrated that whisker stimulation can be used to induce eyeblink response; later, this behavioral paradigm was found to be associated with synaptic patterning changes in the supplementary somatosensory cortex. During my final year of medical school, I was awarded the HHMI-NIH Research Scholar Award.  This award funded my initial work in the laboratory of Dr Zuhang Sheng, in the NINDS (the remainder of my time at NIH was funded by a National Research Scholar Award).  There, my work focused on molecular processes involved in synaptic development and in modulation of presynaptic function.  Specifically, I worked as part of a group that characterized the function of the proteins syntaphilin and syntabulin, the former involved in presynatpic modulation of exo- and endocytosis, and the latter in axonal transport of synaptic components from the cell body to the synapse.  In the process, I learned a broad array of techniques from the fields of genetics, protein biochemistry, cell biology and cell imaging.   Over the last year, I have begun work in the laboratory of Dr John Kessler. My efforts in his lab have been focused on questions pertaining to neuro-oncology; specifically, on the relationship of stem cell biology to tumorigenesis in the adult brain.  My current scientific work is informed by the following long-term interests: 1) To characterize the molecular mechanisms of neural stem cell (NSC) maintenance and proliferation, and to understand how the maintenance of the stem-cell state could create conditions that allow transformation of normal stem cells to glial tumors; and 2) To understand the mechanisms that direct these tumor stem cells to differentiate toward astrocytic or oligodendroglial phenotypes, and perhaps thereby understand why these tumors differ in their biologic behavior. Toward those ends, I have begun work toward the following scientific goals: 1. To isolate and compare stem-like cells from human astrocytic and oligodendroglial tumors. 2. To describe the transcriptional events and molecular mechanisms that account for spontaneous immortalization of NSCs during serial passaging in culture. As a future neurosurgical oncologist, I believe that our ability to treat our patients will finally be restricted by our limited understanding of the basic biology of glial tumors.  Over the next years, I would like to solidify a foundation from which to begin a career as a surgeon and stem cell biologist.  I plan to begin work that can be continued with the assistance of a technician during my final years of residency, and hope to continue that work as an NIH-funded investigator once my training is completed. Publications: Muro, K, Das S., and Raizer, J.J. (2007). Chordomas of the Craniospinal Axis: Multimodality Surgical, Radiation, and Medical Management Strategies. In preparation. Das, S., Ganju, A., Tiel, R.L., and Kline, D.G. (2006). Tumors of the brachial plexus. Accepted for publication in Neurosurgical Review. Das, S., Muro, K., Goldman, S., Rajaraman, V. and DiPatri, A.J. (2007). Medulloblastoma arising from an immature teratoma of the posterior fossa: a case report. J Neurosurg (1 Suppl Pediatrics) 106: 61-64. Yang, B.P., Das, S.., Yang, C.W., and Cozzens, J.W. (2006). Selective invasion of the anterior commissure in glioblastoma multiforme. J Neuro-Onc 80: 275-276. Das, S., Parkinson, P., Novakovic RL, Frank, J., MacDonald, L., and Bendok, B. (2006). Return of sight following trans-arterial coiling of a carotid-cavernous sinus fistula: Case report. Surg Neurol 66: 82-85. Muro, K., Das, S., and Raizer, J.J. (2006). Convection-enhanced and local delivery of targeted cytotoxins in the treatment of malignant gliomas. Technol Canc Res Treat 5: 201-214. Das, S., Chandler, J.P., Pollack, A., Biggio, E., Diaz, J., Raizer, J.A., and Batjer, H.H. (2006). Oligodendroglioma in the pineal region: a case report. J Neurosurg 105: 461-464. Reddy, P., Das, S., Chandler, J.P., and Noskin, G.A. (2006). Stenotrophomonas maltophilia meningitis treated with moxifloxacin: a case report and review of the literature. Infect Dis Clin Pract 14: 173-176. Das, S., Bendok,, B.R., Getch, C.G., Awad, A.A., and Batjer, H.H. (2005). Update on current registries and trials of carotid artery angioplasty and stent placement. Neurosurg Focus. 18: E2, 1-6. Das, S., Parkinson, R., Bernstein, R.A., Alberts, M.J., Shaibani, A., Batjer, H.H., and Bendok, B.R. (2004). Update on carotid artery stenting.  Part I. Contemp Neurosurg 26 (12): 1-7. Das, S., Parkinson, R., Bernstein, R.A., Alberts, M.J., Shaibani, A., Batjer, H.H., and Bendok, B.R. (2004). Update on carotid artery stenting.  Part II. Contemp Neurosurg 26 (13): 1-7. Singh, B.B., Lockwich, T.P., Bandyopadhyay, B.C., Liu, X., Bollimuntha, S., Brazer, S.-C., Combs, C., Das, S., Leenders, A.G.M., Sheng, Z.-H., Knepper, M.A., Ambudkar, S.V., and Ambudkar, I.S. (2004). VAMP2-Dependent Exocytosis Regulates Plasma Membrane Insertion of TRPC3 Channels and Contributes to Agonist-Stimulated Ca2+ Influx. Mol Cell 15: 635-646. Das, S., Boczan, J., Gerwin, C., Zald, P.B., and Sheng, Z.-H. (2003). Regional and developmental regulation of syntaphilin expression in the brain: a candidate molecular element of synaptic functional differentiation. Brain Res Mol Brain Res. 116: 38-49. Das, S., Gerwin, C., and Sheng, Z.-H. (2003). Syntaphilin binds to dynamin-1 and inhibits dynamin-dependent endocytosis. J Biol Chem. 278: 41221-41226. Tian, J.H., Das, S., and Sheng, Z.-H. (2003) Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18. J Biol Chem. 278: 26265-26274. Das, S., Weiss, C., and Disterhoft, J.F. (2001). Stimulation of the mystacial vibrissae in eyeblink conditioning in the rabbit.  Behav Neurosci. 115: 731-736. Bhushan, V., Le, T., Nguyen, H., Amin, C., Das, S., Pall, V. and Grimm, A. (1999). Underground Clinical Vignettes: Behavioral Science: Classical Clinical Cases for USMLE Step 1 Review. Blackwell Science Inc., San Francisco, CA.                                  Gal Finer, MD (PGY4), Department of Pediatrics Information not yet available              Andrew Gawron, MD, PhD (PGY1), Department of Medicine Education: B.S., Truman State University, 1992 M.S., Ph.D., University of Kansas, 1996 Post-doctoral Fellowship, The eppley Cancer Center, University of Nebraska Medical Center M.D., Northwestern University Feinberg School of Medicine Subspecialty Interest:  GI/Oncology Publications: Gawron A.J., Gapstur S.M., Fought A.J., Talamonti M.S., Skinner H.G.  "Sociodemographic and tumor characteristics associated with pancreatic cancer surgery in the United States" submitted to the Journal of Clinical Oncology July 2007. Kohlgraf, K.G., Gawron, A.J., Higashi, M., Meza, J.L., Burdick, M.D., Kitajima, S., Kelly, D.L., Caffrey, T.C., Hollingsworth, M.A. Contribution of the MUC1 tandem repeat and cytoplasmic tail to invasive and metastatic properties of a pancreatic cancer cell line. (Cancer Research, 2003, 63, 5011-20). Kohlgraf, K.G., Gawron, A.J., Higashi, M., VanLith, M.L., Shen, X., Caffrey, T.C., Anderson, J.M., Hollingsworth, M.A. Tumor-specific immunity in MUC1.Tg mice induced by immunization with peptide vaccines from the cytoplasmic tail of CD227 (MUC1).(Cancer Immunol Immunother., 2004, 53, 1068-1084). Gawron, A.J., Martin, R.S., Lunte, S.M. Microchip CE Separations for Biomedical and Pharmaceutical Analysis. (European Journal of Pharmaceutical Sciences, 2001, 14, 1-12) Martin, R.S.; Gawron, A.J.; Fogarty, B.A.; Regan, F.B.; Dempsey, E.; Lunte, S.M. Carbon paste-based electrochemical detectors for microchip capillary electrophoresis/electrochemistry. (The Analyst, 2001, 126, 277-80.) Gawron, A.J.; Martin, R.S.; Lunte, S.M. Fabrication and evaluation of a carbon-based dual-electrode detector for poly(dimethylsiloxane) electrophoresis chips. (Electrophoresis, 2001, 22, 242-48). Gawron, A.J.; Lunte, S.M. Detection of neuropeptides using on-capillary copper complexation and capillary electrophoresis with electrochemical detection. (Electrophoresis, 2000, 21, 3205-11). Martin, R.S.; Gawron, A.J.; Henry, C.S.; Lunte, S.M. Dual Electrode Detection on Poly(dimethylsiloxane)-Fabricated Microchipsâ* (Analytical Chemistry, 2000, 72, 3196-02) Gawron, A.J.; Lunte, S.M. Optimization of the conditions for biuret complex formation for the determination of peptides by capillary electrophoresis with ultraviolet detection.â* (Electrophoresis, 2000, 21, 2067-74) P. J. Hol, A. J. Gawron, J. M. Hurst, A.R. Yeager, D. A. VanGalen, R. Isrenn Investigation of Lead and Cadmium Levels in Roadside Rhododendron Leaves in Bergen, Norway Utilizing Multivariate Analysis. (Microchemical Journal: Undergraduate Research Special Issue, 1997, 55, 169-178)

Laleh Golkar, MD (PGY6), Department of Surgery

Information not yet available

Brian Helfand, MD, PhD (PGY3), Department of Urology

Education:

B.S., EmoryUniversity, 1999
M.D., Ph.D., Northwestern University Feinberg School of Medicine, 2005

Research Interests:

My current research interests are focused on intermediate filament (IF) proteins and their dynamics and involvement in urothelial cell metastasis and cell motility. For many years textbooks described IFs as very stable and rigid structures, only recognized for their maintenance of the mechanical stability of cells. However, the results of live cell imaging studies demonstrate the opposite. These studies have shown that IF networks are active and dynamic components of the cytoskeleton.  The dynamic properties of IF may lend novel properties to cells which permit motility.  Therefore, my research goals are to determine how IF contribute to metastatic behavior.  In addition, my research is also focused upon the utility of IF as markers for predicting metastatic disease.

The first studies revealing the dynamic properties of IF employed the use of fluorescence recovery after photobleaching (FRAP). These studies revealed that there was constant subunit exchange between subunits and polymerized IF. They also revealed that IF were not polarized with respect to subunit exchange as recovery took place at equal rates all along the length of the photobleached zones. Other studies involving GFP-tagged IF proteins have demonstrated motility of different structural forms of IF within cells.  For example, fast IF movements have been described in spreading fibroblasts which are enriched in non-filamentous precursors to mature IF, known as IF particles. These IF particles move bidirectionally along microtubule tracks at speeds up to ~1-2 um/min through interactions with the molecular motors, kinesin and dynein. Many of these particles assemble into short IF termed “squiggles” which in turn form the longer “filaments” found in established IF networks. Even the extensively polymerized IF networks of spread cells move, albeit more slowly, and many individual filaments appear to be constantly altering their shapes. Unlike faster particle and squiggle movements, these changes in shape, which frequently appear like propagated waves, do not require interactions with microtubules and/or microfilaments, suggesting that there are intrinsic, albeit unknown, regulatory factors responsible for some aspects of IF motility.

At first glance there would appear to be a gap between studying IF motility and urologic disease.  However, IF proteins have historically been used by urologists as markers of metastatic disease.  For example, aggressive urothelial tumors often express vimentin when these cells transform into a metastatic phenotype. 

Prostate cancer is the most common malignancy afflicting males in the United States.  While localized tumor growth in the prostate is certainly a disease associated with significant morbidity and large health care costs, cell metastasis from the primary tumor site is responsible for the most insidious complications of prostate cancer and its mortality.  Early identification of metastatsis is important because it changes the clinical management of prostate cancer from surgical to medical and affects the long term prognosis of the patient.  Currently, pathologists use the Gleason scoring system to grade tumors obtained from both transrectal ultrasound guided prostate biopsies and specimens obtained from radical prostatectomy.  The Gleason score is based exclusively on the architectural pattern of the glands of the prostate tumor. It evaluates the overall appearance of prostate tumor cells and the degree to which they resemble normal prostate cells. Gleason grading extends from very well differentiated (grade 1) to very poorly differentiated (grade 5),  as determined by observing cells microscopically at low magnification and evaluating changes in their overall shape as well as the shape of their nuclei.  In general, the Gleason score can be correlated with survival time (i.e. lower Gleason scores are associated with improved outcomes). However, prostate cancer is a very complicated disease, and patients with low Gleason scores sometimes fare poorly, while men with high Gleason scores have been known to do well. Significant improvements in disease management have occurred when the Gleason score is combined with other indicators of disease (e.g. serum prostate specific antigen level).  However, additional prognostic markers are desperately needed to improve management of prostate cancer of all stages.

As mentioned above, the Gleason score takes advantage of the fact that prostate carcinoma cells have alterations in their cell and nuclear shape.  In general, the typical cuboidal morphology of epithelial cells changes to an elongated shape resembling a mesenchymal cell or fibroblast.  In many other types of epithelial-derived cancers (such as breast and lung cancer), this shape change is referred to as the epithelial-mesenchymal transition (EMT) and it is a prelude to the migration of cells to other tissues.  While the EMT in prostate cancer has been suggested, it has not been documented ⁶.  I have preliminary evidence indicating that the EMT occurs in prostate cancer and that it is associated with the abnormal expression of cytoskeletal and nuclear intermediate filaments (IF).  While recent evidence has shed light on the function of these IF proteins in normal cells, little is known about their role in the EMT and in particular their role in prostate cancer.  Furthermore, their utility as predictors of metastatic disease has never been investigated.      

Silver, R.K., Russell, T.L., Brodin, A.G., Check, I.J., Helfand B.T., Caplan, M.S. (1998) Variability of Murine Pregnancy Outcome Resulting from Passive Immunization with Anticardiolipin Antibody-Positive Immunoglobulin G. J Matern Fetal Investig. Mar;8(1):35-8.

Prahlad, V., Helfand B.T., Langford, G.M., Vale, R.D., Goldman, R.D. (2000) Fast transport of neurofilament protein along microtubules in squid axoplasm.  J Cell Sci. 112(22): 3939-3946.

Chou, Y.H., Helfand B.T., Goldman, R.D. (2001) New horizons in cytoskeletal dynamics: Transport of intermediate filaments along microtubule tracks.  Curr Opinion Cell Biol. 13(1): 1106-1109.

Helfand B.T., Mikami, A., Vallee, R.B., Goldman, R.D.  (2002) A Requirement for cytoplasmic dynein and dynactin in the organization and maintenance of intermediate filament networks.  J Cell Biol. 157(5): 795-806.

Helfand B.T., Mendez, M.G., Pugh, J., Delsert, C., Goldman, R.D.  (2003) A role for intermediate filaments in determining and maintaining the shape of nerve cells. Mol Biol Cell. Dec;14(12):5069-81.

Helfand B.T., Chang, L., Goldman, R.D. (2003) The dynamic and motile properties of intermediate filaments.  Ann Review of Cell and Develop Biol. 19: 445-467.

Helfand B.T., Loomis, P., Yoon, M., Goldman, R.D.  (2003) Rapid transport of the neuronal intermediate filament protein, peripherin, in PC12 cells.  J Cell Sci. 116(11): 2345-2359.

McGovern, S.L., Helfand B.T., Feng, B., Shoichet B.K. (2003) A specific mechanism of non-specific inhibition. J Med Chem. 46(20): 4265-4272.

Helfand B.T., Chang L., Goldman, R.D.  (2004) Intermediate filaments are dynamic and motile elements of cellular architecture.  J Cell Sci. Jan 15:117(Pt 2):133-41.

Helfand B.T., Chou, Y.H., Shumaker, D.K., Goldman, R.D. (2005) Intermediate filament proteins participate in signal transduction.Trends Cell Biol. Nov;15(11): 568-70.

Hillberg, L., Zhao, R, L.S., Nyakern-Meazza, M., Helfand B.T., Goldman, R.D., Schutt, C., Lindberg, U. (2006) Tropomyosins are present in lamellipodia of motile cells.  Euro J Cell Biol. 85 (5): 399-409.

Helfand B.T., Mouli, S., Dedhia, R., McVary, K.T. (2006)  Management of lower urinary tract symptoms secondary to benign prostatic hyperplasia with open prostatectomy- results of a contemporary series.  J Urol. (in press).

Helfand,  B.T., Chang, L., Khuon, S., Herrmann, H., Aebi, U., Goldman, R.D.,  (2006)  Vimentin intermediate filaments function stabilize lamellipodial activity and promote cell motility.  J Cell Biol. In Preparation.

Silver, R.K., Helfand B.T., Russell, T.L., Ragin A., Sholl, J.S., MacGregor, S.N.  (1995)  Multifetal reduction     increases the risk of preterm deliver and fetal growth restriction in twins.  Dept. of Ob/Gyn, Evanston Hospital, Evanston, IL.   American Gynecological and Obstetric Society.

Silver R.K., Russell, T.L., Mullen, T..Kambich M., Leeth E., Helfand B.T., MacGregor, S., Sholl, J. (1995)   Prosepective Evaluation of Early Mid-Trimester Amniocentesis.  Dept. of Ob/Gyn, Evanston Hospital, Evanston, IL.  Society for Perinatal Obstestrics.

Silver, R.K., Russell, T.L., Brodin, A.G., Check, I.J., Helfand B.T., Caplan, M.S. (1995)  Murine antiphospholipid syndrome resulting from pooled versus single-donor antibody-positive sera. Depart. of Ob/Gyn, Evanston Hospital, Evanston, IL.  Society for Perinatal Obstestrics.

Helfand B.T. and Edwards D.A. Lateral tegmental control of copulation in the male rat. (1996) Summer
      Undergraduate Program Howard Hughes at Emory.  Atlanta, Georgia.

Helfand B.T., Greco, B., Edwards, D.A. (1997) Distribution of androgen receptor-immunoreactive and mating-induced Fos-immunoreactive neurons in the hindbrain of male rats.  Society for Behavioral Neuroendocrinology and Conference on Reproductive Behavior. Baltimore, Maryland

Helfand B.T. and Edwards, D.A. (1998). Distribution of androgen receptor-immunoreactive and mating- induced Fos-immunoreactive neurons in the hindbrain of male rats.  Honors Thesis Presentation.  Emory University, Atlanta, Georgia.

Bardenstein, R., Helfand B.T., Buchanan, C., Chez, M.G. (1998) Improvement in EEG and clinical function in pervasive developmental delay (PDD):  Effect of valproic acid.  Epilepsia;  38.

Helfand B.T., Bardenstein, R., Buchanan C., Chez, M.G. (1998) Improvement in EEG and clinical function in pervasive developmental delay (PDD): Pharmacological effects of monotherapy and combination therapy using valproic acid and predinisone.  Epilepsia; 39. 

Helfand B.T., Prahlad, V. and Goldman, R.D. (2000).  Fast transport of neurofilament proteins along microtubules in squid axoplasm.  1st International Symposium, “Cellular and Molecular Aspects of the Birth, Life, and Death of the Nervous System”, Pucon, Chile.

Goldman, R.D., Goldman, A.E., Chou, Y.-H., Spann, T.P., Moir, R.M., Loomis, P., Linz, L., Yoon, K.-H., Khuon, S., Lopez-Soler, R., and Helfand B.T. (2001).  The dynamic properties of intermediate filaments: implications for healthy and diseased cells.  French-American Colloquium on the Cytoskeletal and Human Disease, Marseille, France.

Helfand B.T., Mikami, A., Vallee, R.B. and Goldman, R.D. (2001).  A requirement for cytoplasmic dynein in vimentin organization.  41st ASCB Annual Meeting, Washington, DC.  Molecular Biology of the Cell, 12: 287a.

Goldman, R.D., Khuon, S., Yoon, M., Helfand B.T., Aebi, U. and Herrmann, H. (2001).  The structure and function of intermediate filament proteins in the lamellipodia and ruffled membranes of cultured cells.  41st ASCB Annual Meeting, Washington, DC.  Molecular Biology of the Cell, 12: 293a.

Helfand B.T. and Goldman, R.D. (2002) Peripherin transport and neurodegenerative disease.  MSTP National Conference.  Aspen, CO.

Goldman, R.D., Khuon, S., Chang, L., Helfand B.T., Aebi, U. and Herrmann, H. (2002).  Vimentin particles are located in lamellipodia and ruffled membranes:  Implications for cell locomotion, and signal transduction.  Gordon Research Conference on Intermediate Filaments. Roger Williams University.  Bristol, RI.

Helfand B.T., Loomis, P. and Goldman, R.D. (2002). The peripherin express:  A neural IF protein transport system with few stops. Gordon Research Conference on Intermediate Filaments. Roger Williams University, Bristol, RI.

Helfand B.T., Chang, L., Kreplach, L., Goldman, R.D. (2002).  In vitro systems to determine the mechanisms of intermediate filament motility.  42nd ASCB Annual Meeting, San Francisco.  Molecular Biology of the Cell. 13:290b

Helfand B.T., Mendez, M.G., Pugh, Delsert, C., and Goldman, R.D. (2003). Intermediate filaments are important in determining the shape and function of nerve cells.  43rd ASCB Annual Meeting, San Francisco.  Molecular Biology of the Cell. 14:314.

McVary, K.T., Helfand B.T., Roehrborn, C.G., Donnell, R.F., Bruskewitz, R., Kaplan, S.A., Kusek, J.W., Coombs, L. (2005). Variation in IRB review of a multi-center clinical trial study protocol.  American Urological Association (AUA) Annual Meeting; San Antonio, TX.

Helfand,  B.T., Chang, L., Khuon, S., Herrmann, H., Aebi, U., Goldman, R.D.,  (2006)  Vimentin intermediate filaments function stabilize lamellipodial activity and promote cell motility. 46th ASCB Annual Meeting, San Francisco.  Molecular Biology of the Cell

Loeb, S., Roehl, K.A., Graif, T.M., Viprakasit, D.P., Gashti, S.N., Thaxton, C.S., Helfand B.T., Catalona, W.J. (2007) Percentage and tumor characteristics of patients who develop undetectable PSA levels after salvage radiotherapy. American Urological Association (AUA) Annual Meeting, Annaheim, CA.

Helfand B.T.,  Loeb, S., Anderson, C.B., Cashy, J., Meeks, J.J. Thaxton, C.S., Roehl, K.A., Catalona, W.J. (2007)  PSA velocity in men with prostatitis documented on the biopsy specimen or prostatectomy specimen.  American Urological Association (AUA) Annual Meeting, Annaheim, CA.

Thaxton, S.A., Loeb, S., Roehl, K.A., Helfand B.T., Meeks, J.J., Catalona W.J. (2007) PSA velocity in screened versus referred men with prostate cancer. American Urological Association (AUA) Annual Meeting, Annaheim, CA.

Helfand B.T., Vyas, A., Fine, M., Dedhia R., Anderson, C.B., McVary, K.T. (2007) Post-operative PSA values and PSA velocity predict the presence of prostate cancer following various surgical interventions for benign prostatic hyperplasia (BPH). American Urological Association (AUA) Annual Meeting, Annaheim, CA.

Helfand B.T., Loeb, S., Cashy, J., Roehl, K.A., Graif, T., Han, M., Catalona, W.J. (2007) Tumor characteristics and treatment outcomes of carriers and noncarriers of the DECODE prostate cancer susceptibility genes. American Urological Association (AUA) Annual Meeting, Annaheim, CA.

Pazona, J.F., Thaxton, C.S., Helfand B.T., Zhoa, L.C., Smith, N. (2007) Neuroligand is a novel marker of prostate cancer. American Urological Association (AUA) Annual Meeting, Annaheim, CA.

Helfand B.T., Moon, T.D., McVary, K.T. (2006)  Medical management of benign prostatic hyperplasia.  Atlas of the Prostate. 3rd Ed; Current Medicine LLC. Ed Scardino and Slawin.

Helfand B.T. and McVary, K.T. (2006) Complications of minimally invasive surgery. Urologic Surgery. Current Medicine LLC. Ed. Scardino.

Helfand B.T. and McVary, K.T. (2007) Contemporary diagnosis and management of benign prostatic hyperplasia (BPH). 1rst Ed; Handbooks in Healthcare Co., Newton, PA.

Meeks, J.J., Helfand, B.T., Nadler, R.B. (2007) Retrieval of migrated ureteral stent by intussception with flexible ureteroscopic basket. J Endourology (submitted)

Helfand, B.T., Khoun, S., Chang, L., Goldman, R.D. (2007) Vimentin structures are components of lamellipodia and are required for cell migration.  J Cell Biol. (in preparation)
     

.

Melissa Hogg, MD (PGY4), Department of Surgery

Education:

B.S., University of Notre Dame, Biochemistry, 2000
B.A., University of Notre Dame, Film and Television, 2000
M.D., Northwestern University Feinberg School of Medicine, 2004

Research Interests:

Dr. Hogg’s research is in Dr. Kibbe’s laboratory which is focused on nitric oxide and its ability to decrease the neointimal hyperplasia that ensues following vascular surgery procedures leading to re-stenosis.  Specifically Melissa will be looking at the role of estrogen and alpha and beta estrogen receptors.  She is attempting to prove that estrogen mediates its vasoprotective properties by modulating NO production, either through transcriptional or post-translational modification of NOS enzymes or through modulating signal transduction pathways known to regulate NO production.  This data with eventually be incorporated into translational research from the laboratory which is developing nitric oxide-based therapies for the prevention of neointimal hyperplasia following vascular procedures in hopes of targeting women specifically for improved outcomes. 

Publications:

Hogg, ME, Kibbe, MR. “Percutaneous Thoracic and Abdominal Aortic Aneurysm Repairs:  Technique and Outcomes.” Vascular 2006:14(5):270-281.

Hogg, ME, Peterson, BG, Pearce, WH, Morasch, MD, Kibbe, MR. “Bare Metal Stent Infection:  Case Report and Review of the Literature.” Journal of Vascular Surgery 2007 (In press).

Book Chapters

Hogg ME, Kibbe MR.  Treatment of Infected Bare Metal Stents: The Naked Truth about Problems Bugging our Patients. In Operative Vascular Surgery in the Endovascular Era.  Pearce WH, Matsumura JS, Yao JST, Eds. Greenwood Academic, Chicago, IL, 2007.(In press).

Janette Holub, MD (PGY4), Department of Surgery

          Education:

          BA, Valparaiso University 2001
          MPH (Health Policy and Administration), University of Illinois College of Medicine 2005
          MD, University of Illinois College of Medicine 2005

Research Interests:

Dr Holub is currently a research fellow under the mentorship of Dr Mary Beth Madonna, whose lab at the Childrens Memorial Research Center focuses on the study of neuroblastoma, the most common extra-cranial solid cancer of childhood and  responsible for 15% of all cancer deaths in children. As neuroblastoma tumors are derived from neural crest cells they respond to neuronal growth factors, including nerve growth factor (NGF). Alterations in the receptors for NGF (Trk A and p75) have been shown to influence the clinical behavior of neuroblastoma tumors. Previous studies have illustrated that neuroblastoma cells transfected with the Trk A receptor and stimulated with NGF undergo differentiation, resulting in a less aggressive behavior. NGF also exerts its efffects via a low affinity p75 receptor. Prior investigations have demonstrated that neuroblastoma cells expressing the p75 receptor show a high degree of apoptosis that is inhibited when these cells are transfected with the Trk A receptor. Recent work in this lab has determined that Trk A receptor expression in a NGF-transfected cell line that demonstrates less aggressive characteristics was equivalent to that in a wild type cell line but that p75 expression was significantly higher in the less aggressive NGF-transfected cell line.

Summary Objective:
After transfecting the SK-N-SH wild type cell with the p75 receptor, these cells will then be stimulated with nerve growth factor to determine the effects on cell growth and apoptosis, as well as delineate the signaling pathway by which NGF exerts its effects and if the p75 receptor plays a role in this process.

Specific Aims:
1. To confirm that activation of the p75 low affinity nerve growth factor receptor induces human nueroblastoma cells to undergo apoptosis.
2. To delineate the pathways that are activated by the interaction of NGF and the p75 receptor with an emphasis on the p38 pathway.
3. To test the hypothesis that drugs targeting this specific receptor will suppress neuroblastoma growth in vivo and improve prognosis.
4. To determine if Trk A receptor inhibition will force cells into apoptosis via the p75 receptor pathway.       

Abstracts/Presentations:   

 J Holub, C Pabin, M N Lutiyya.  “US Adolescent Physical Injury Sustained from Physical Fighting: An Analyisis of 2003 Youth Risk Behavior Survey Data.”  University of Illinois College of Medicine, 10th Annual Research Day, Rockford, IL March 2005.

K Ramaswamy, M Gnanasekar, V Vidhya, J Holub, and Y X He.  "Molecular characterization of a novel receptor for IgE-independent histamine releasing factor on the surface of basophils."  12th International Congress of Immunology, Montreal, Quebec, Canada July 2004.

J Holub, C Pabin, M N Lutfiyya.  "Provision of preventive health services: A comparison of 2001 NAMCS and BRFSS data."  University of Illinois College of Medicine 2004 Student Medical Research Forum, Chicago, IL January 2004.

J Holub, V Viswanathan, G Munirathinam, L Frenkel, H Zietz, R Kalyanasundaram.  "Discovery of a novel histamine releasing receptor and its clinical correlation to allergy and asthma in the human."  University of Illinois College of Medicine, 8th Annual Research Day, Rockford, IL April 2003.

Wenya Huang, MD (PGY1), Department of Medicine Education: PhD: Northwestern University, Nueroscience (2007) MD: Beijing Medical University (1998) Subspecialty Interest(s): Endocrinology

Publications

Huang W. Qiu J. Ronnekliev OK. Levine JE. ATP sensitive potassium channels are expressed in GnRH neurons and regulate GnRH pulse generator activity. (manuscript in preparation)

Shi X. Huang W. Wang Z. Preservation of the hypothalamic structures in the total resection of craniopharyngioma. Chinese Medical Science Journal. 16:218-22; 2001 Dec.

Huang W. Shi X. Treatment of sodium disorders after surgery of cranioopharyngiomas. Chinese Medical Science Journal. 15:246-8; 2000 Dec.

Colleen Jay, MD (PGY3), Department of Surgery

Information not yet available

Nils Johnson, MD (PGY4), Department of Medicine

Education:

B.S., University of British Columbia, physics and computer science, 2000
M.D., Columbia University, 2004
Subspecialty interest:  Cardiology

Research Interests:

Johnson NP, Denes P. Abstract The ladder diagram (a 100+ year history). American Journal of Cardiology 101(12):1801-1804, 15 June 2008. [PMID: 18549863]

Gould KL, Pan T, Loghin C, Johnson NP, Sdringola S. Reducing radiation dose in rest-stress cardiac PET/CT by single poststress cine CT for attenuation correction: quantitative validation. Journal of Nuclear Medicine 49(5):738-745, May 2008. [PMID: 18413384]

Gould KL, Pan T, Loghin C, Johnson NP, Guha A, Sdringola S. Frequent Diagnostic Errors in Cardiac PET/CT Due to Misregistration of CT Attenuation and Emission PET Images: A Definitive Analysis of Causes, Consequences, and Corrections. Journal of Nuclear Medicine 48(7):1112-1121, July 2007. [PMID: 17574974]

Johnson NP, Gould KL. Clinical Evaluation of a New Concept: Resting Myocardial Perfusion Heterogeneity Quantified by Markovian Analysis of PET Identifies Coronary Microvascular Dysfunction and Early Atherosclerosis in 1,034 Sub jects. Journal of Nuclear Medicine 46(9):1427-1437, September 2005. [PMID: 16157524]

Johnson NP. Advantages to Transforming the Receiver Operating Characteristic (ROC) Curve into Likelihood Ratio oordinates. Statistics in Medicine 23(14):2257-2266, 30 July 2004. [PMID: 15236429]

Johnson NP. The Brachistochrone Problem. College Mathematics Journal (CMJ) 35(3):192-197, May 2004.

Muneera Kapadia, MD (PGY6), Department of Surgery

Education:

B.S., Massachusetts Institute of Technology, Chemical Engineering, 1998
M.D., University of Michigan Medical School, 2002

Research Interests:

The focus of our lab is to develop nitric oxide-based therapies for the prevention of neointimal hyperplasia following vascular procedures. In addition, I am studying the effects of nitric oxide on the ubiquitin-proteasome pathway in an effort to better understand the effect of nitric oxide on neointimal hyperplasia on a molecular and cellular level.

Publications:

Kapadia MR, Najjar SF, Kibbe MR.  Trends in Vascular Surgery.  “Nitric Oxide-Based Therapies in Vascular Disease.”  2005: 147-160.

Yang J, Motlagh D, Allen JB, Webb AR, Kibbe MR, Aalami O, Kapadia M, Carrolli TJ, Guillermo AA.  “Advanced Materials.”  Improving vascular graft biocompatibility via the interfacial in-situ polycondensation of a citric acid-based biodegradable elastomer.  2006.

Kapadia MR, Popwich DA, Kibbe MR.  Trends in Vascular Surgery.  “Modified Prosthetic Vascular Conduits.”  In press.
Abstracts/Presentations

Kapadia M, Aalami O, Jiang Q, and Kibbe M.  Nitric Oxide Reversibly Inhibits the PA28 Activator Via S-Nitrosylation. Poster at the Society for Free Radical Biology and Medicine meeting, November 2005.

Najjar SF, Pearce C, Eng J, Aalami O, Kapadia M, Lyle B, Murar J, Jiang Q, and Kibbe MR.  Efficacy of Perivascular NO-Eluting Therapies for the Prevention of Neointimal Hyperplasia.  Presented at the Association for Academic Surgery meeting, February 2006.

Kapadia M, Aalami O, Najjar SF, Jiang Q, and Kibbe MR.  Nitric Oxide-Mediated Inhibition of the PA28 Proteasome Activator.  Presented at the Society for University Surgeons meeting, February 2006.

Aalami OO, Kapadia MR, Najjar SF, Jiang Q, Zuckerbraun B, Kibbe MR.  The Role of p53 and Heme Oxygenase in Regulating Nitric Oxide-Induced Apoptosis of Vascular Smooth Muscle Cells.  Presented at the Society for Vascular Surgery Research Initiatives Conference, March 2006.

Abstracts/Presentations:

Kapadia, MR, Aalami, OO, Jiang, Q and Kibbe MR.  The Role of Nitric Oxide in Regulating Caspase-like Activity of the 26S Proteasome.  Poster at the Nitric Oxide Society Meeting, June 2006.

Aalami, OO, Kapadia, MR, Jiang, Q and Kibbe MR.  The Role of p53, Nitric Oxide and Reactive Oxygen Species in Vascular Smooth Muscle Cell Apoptosis.  Presented at the Nitric Oxide Society Meeting, June 2006.

Yang, J, Motlagh D, Allen J, Webb AR, Kibbe MR, Aalami O, Kapadia M, Carroll TJ, Ameer G.  Poly-(Diol Citrate)-Mediated Functionalization of ePTFE Grafts.  Poster at the Biomedical Engineering Society Meeting, October 2006.

Yang J, Motlagh D, Allen JB, Webb AR, Kibbe M, Aalami O, Kapadia M, Carroll TJ, and Ameer GA.  Improving the Biocompatibility of Expanded Polytetrafluoroethylene Vascular Graft via a Novel Biodegradable Elastomer. Presented at the American Institute of Chemical Engineers Meeting, November 2006.

Kapadia, MR, Aalami, OO, Jiang Q, Elhofy A, Kibbe MR.  Nitric Oxide Inhibits the 26S Proteasome in Six Cell Types Important in the Vasculature.  Presented at the American College of Surgeons Surgical Forum Meeting, October 2006.

Kapadia, MR, Flannery WD, Rossi NB, Jiang Q, Kibbe MR.  Nitric Oxide Inhibits De-Ubiquitination by Isopeptidase T.  Accepted for presentation at the Academic Surgical Congress, February 2007.

Kapadia, MR, DaRosa, DA, MacRae, HM, Dunnington, GL.  Survey of Surgical Skills Laboratory.  Accepted for presentation at the Association of Program Directors in Surgery Meeting, April 2007.

Kapadia, MR, Melstrom, LG, Halverson, AL.  Presentation and Treatment Outcomes of Anal Condyloma.  Submitted to the American Society of Colon and Rectum Surgeons Meeting, 2007.

Kapadia, MR, Chow, LW, Ahanchi, SS, Eng, J, Murar, J, Martinez, J, Tsihlis, ND, Popowich, DA, Jiang, Q, Hulvat, JF, Stupp, SI, Hrabie, JA, Saavedra, JE, Keefer, LK, Kibbe, MR.  Nanotechnology and Nitric Oxide: A Novel Approach to Inhibit Neointimal Hyperplasia.  Submitted to the Society for Vascular Surgery Meeting, 2007.

Dae Kim, MD (PGY1), Department of Urology Information not yet available

Brian Layden, MD, PhD (PGY3), Department of Medicine

Education:

B.S., Loyola University, Psychology, 1997
Ph.D., Loyola University, Chemistry, 2001
M.D., University of Illinois at Chicago, 2005

Research Interests:

During graduate school, I performed research studying the biochemical mechanism of lithium treatment in bipolar illness under the guidance of Duarte Mota de Freitas, Ph.D.  One proposed mechanism of therapeutic action is that lithium exerts its effects by competing with magnesium for binding sites within the cell.  One of my first studies involved developing techniques to examine this competition.  Next, I demonstrated that this competition was observable within neuronal cells.  Follow-up studies demonstrated that this competition could be observed under therapeutic and chronic lithium treatment conditions in neuronal cells.  In additional studies, I identified the major lithium binding sites within neuronal cells and how chronic treatment with lithium can alter these sites by regulating different phospholipid pathways. 

During medical school, I performed research in the laboratory of Mark M. Rasenick, Ph.D.  My research in this laboratory focused on studying the interaction between guanine nucleotide binding proteins (G proteins) and tubulin, two proteins that have been linked to the mechanism in which antidepressant assert their effect.  Further, this novel interaction is important because this protein complex can result in the destabilization of microtubules and receptor-independent activation of G proteins.  My role in this project was to define the three dimensional structure of this protein interaction.  In my first project, I used peptide arrays to show potential binding sites between the proteins and then, using molecular modeling techniques, predicted the first three dimensional model of this interaction.  In an additional project, using fluorescent-labeled G proteins, I examine how this interaction results in structural changes in the G proteins, providing insight into how G proteins may be activated by tubulin.  Currently, at Northwestern University, I will also be working on a joint project with Dr. Rasenick and Dr. Douglas Freymann in which we will attempt to make and analyze crystals of the complex between tubulin and one particular G protein.  By studying this interface between these two molecules, we hope to generate a novel antidepressant compound.  Following residency, my research goals are to focus on studying the interface between the central nervous system and the regulation of endocrine pathways in the body.

Publications:

Montezinho LP. B Duarte C. Fonseca CP. Glinka Y. Layden B. Mota de Freitas D. Geraldes CF. Castro MM. Intracellular lithium and cyclic AMP levels are mutually regulated in neuronal cells. Journal of Neurochemistry. 90(4):920-30, 2004 Aug.

Layden BT. Minadeo N. Suhy J. Abukhdeir AM. Metreger T. Foley K. Borge G. Crayton JW. Bryant FB. de Freitas DM. Biochemical and psychiatric predictors of Li(+) response and toxicity in Li(+)-treated bipolar patients. Bipolar Disorders. 6(1):53-61, 2004 Feb.

Williams N. Layden BT. Suhy J. Metreger T. Foley K. Abukhdeir AM. Borge G. Crayton J. Bryant FB. Mota de Freitas D. Testing competing path models linking the biochemical variables in red blood cells from Li+-treated bipolar patients. Bipolar Disorders. 5(5):320-9, 2003 Oct.

Diven CF. Wang F. Abukhdeir AM. Salah W. Layden BT. Geraldes CF. Mota de Freitas D. Evaluation of [Co(gly)3]- as a 35Cl- NMR shift reagent for cellular studies. Inorganic Chemistry. 42(8):2774-82, 2003 Apr 21.

Abukhdeir AM. Layden BT. Minadeo N. Bryant FB. Stubbs EB Jr. Mota de Freitas D. Effect of chronic Li+ treatment on free intracellular Mg2+ in human neuroblastoma SH-SY5Y cells. Bipolar Disorders. 5(1):6-13, 2003 Feb.

Minadeo N. Layden B. Amari LV. Thomas V. Radloff K. Srinivasan C. Hamm HE. de Freitas DM. Effect of Li+ upon the Mg2+-dependent activation of recombinant Gialpha1. Archives of Biochemistry & Biophysics. 388(1):7-12, 2001 Apr 1.

Layden B. Diven C. Minadeo N. Bryant FB. Mota de Freitas D. Li+/Mg2+ competition at therapeutic intracellular Li+ levels in human neuroblastoma SH-SY5Y cells. Bipolar Disorders. 2(3 Pt 1):200-4, 2000 Sep.

Amari L. Layden B. Rong Q. Geraldes CF. Mota de Freitas D. Comparison of fluorescence, (31)P NMR, and (7)Li NMR spectroscopic methods for investigating Li(+)/Mg(2+) competition for biomolecules. Analytical Biochemistry. 272(1):1-7, 1999 Jul 15.

Amari L. Layden B. Nikolakopoulos J. Rong Q. Mota de Freitas D. Baltazar G. Castro MM. Geraldes CF. Competition between Li+ and Mg2+ in neuroblastoma SH-SY5Y cells: a fluorescence and 31P NMR study. Biophysical Journal. 76(6):2934-42, 1999 Jun.

Brian Le, MD (PGY1), Department of Urology Information not yet available

John Linn, MD (PGY3), Department of Surgery

Information not yet available

Robroy MacIver, MD (PGY6), Department of Surgery

Information not yet available

Kristina A. Matkowskyj, MD, PhD (PGY1), Department of Pathology Education: BS: University of Illinois at Urbana/Champaign, Specialized Chemistry (1997) PhD: University of Illinois at Chicago, Pathology (2002) MD: University of Illinois at Chicago (2007) Subspecialty Interest(s): GI Oncology

Research Interests:

I conducted my graduate research in the laboratory of Dr. Richard V. Benya, MD.  The major research focus of the laboratory concerns the processing and regulation of heptaspanning, G protein-coupled receptors; specifically, the receptors for gastrin-releasing peptide and galanin.
 
Prior to the start of graduate and medical school, my investigations focused on the gastrin-releasing peptide receptor (GRP-R).  My efforts focused on developing a novel algorithm for true quantitative immunohistochemistry (Q-IHC) based on calculating the cumulative signal strength, or energy, of the digital file encoding an image and to determine the absolute amount of chromogen present per pixel.  Our efforts enabled us to use Q-IHC to accurately determine the amount of peptide hormone receptor in archived tissues.  To this end, we set out to determine the expression and role of the GRPR protein in the gastrointestinal tract.  This receptor is known to cause the proliferation of many, but not all cells in which it is expressed.  Our studies identified that this receptor is not normally expressed by epithelial cells lining the GI tract, but is aberrantly expressed by many GI malignancies.  Additional studies support GRPR acting as a mitogen, and recent data supports that in vivo it may behave as a morphogen.
 
The primary focus of my graduate research work was investigating the role of the galanin-1 receptor (Gal1R) in the context of infectious diarrhea.  It is known that galanin is widely expressed in the central nervous system and in the GI tract by enteric nerves.  In in the GI tract, galanin receptors are expressed by smooth muscle cells which when activated modulate intestinal transit.  We have shown that epithelial cells lining the human GI tract express only GalR1 and when activated results in chloride secretion from these cells.  Gal1R expression is transcriptionally regulated by the inflammation-associated transcription factor NF-kappa B, a factor activated in a number of inflammatory states.  We have shown that an increase in Gal1R expression is observed in various infalmmatory conditions such as Crohns disease, ulcerative colitis, and infectious colitis.  It is thus hypothesized that Gal1R expression and activation represents a common, unifying pathway accounting for the diarrhea associated with inflammatory conditions affecting the colon.
 
My future research goals include further study into the biology of gastrointestinal malignancies occuring in patients with various inflammatory conditions

Publications:

Matkowskyj KA, Nathaniel R, Prasad R, Rao MC, Benya RV. Age-dependent differences in response to salmonella infection are due to alterations in galanin-1 receptor (Gal1-R) expression.  [in preparation]

Hempson S, Matkowskyj KA, Bansal A, Tsao E, Habib I, Benya RV, Shaw RD. Rotavirus infection of small intestine causes colonic secretion through regulation of galanin-1 receptor.  [submitted]

Taglia L, Matusiak D, Matkowskyj KA, Benya RV.  Gastrin-releasing peptide mediates its morphogenic properties in human colon cancer by up-regulating intracellular adhesion protein-1 (ICAM-1) via focal adhesion kinase. Am J Physiol Gastrointest Liver Physiol 2007; 292(1): G182-90.

Savkovic SD, Villanueva J, Turner JR, Matkowskyj KA, Hecht G.  Mouse model of enteropathogenic Escherichia coli infection. Infect Immun 2005; 73(2):1161-70.

Matusiak D, Glover S, Nathaniel R, Matkowskyj K, Yang J, Benya RV.  Neuromedin B and its receptor are mitogens in both normal and malignant epithelial cells lining the colon.  AJP Gastro 2005; 288(4): G718-28.

Matkowskyj KA, Glover S, Benya RV. Quantitative immunohistochemistry (Q-IHC): A novel algorithm for measuring cumulative signal strength and predicting receptor number. Microscopy & Analysis 2004; 18: (issue #66) 5-6.

Matkowskyj KA, Nathaniel R, Prasad R, Weihrauch D, Rao M, Benya RV. Galanin contributes to the excess colonic fluid secretion observed in dextran sulfate sodium murine colitis.  Inflammatory Bowel Dis 2004; 10: 408-416.

Matkowskyj KA, Keller K, Glover S, Kornberg L, Tran-Son-Tay R, and Benya RV.  Expression of GRP and its receptor in well differentiated colon cancer cells correlates with the presence of focal adhesion kinase phosphorylated at tyrosines 397 and 407. J Histochem Cytochem  2003; 51, 1041-1048.

Matkowskyj KA, Schonfeld D, Benya RV.  Quantitative immunohistochemistry by measuring cumulative signal strength accurately measures receptor number. J Histochem Cytochem 2003; 51, 205-214.

Carroll RE, Matkowskyj K, Saunthararajah Y, Sekosan M, Battey JF, Benya RV.  Contribution of gastrin-releasing peptide and its receptor to villus development in the murine and human gastrointestinal tract. Mech Dev 2002; 13:121-30.

Matkowskyj KA, Danilkovich A, Marrero JA, Savkovic S, Hecht G, Benya RV. Galanin-1 receptor up-regulation mediates the excess colonic fluid production caused by infection with enteric pathogens.  Nature Med 2000; 6: 1048-1051.

Carroll RE, Matkowskyj KA, Tretiakova MS, Battey, JF, Benya RV.  Gastrin-releasing peptide is a mitogen and morphogen in murine colon cancer.  Cell Growth Diff 2000; 11: 385-393.

Marrero JA, Matkowskyj KA, Yung K, Hecht G, Benya RV. Dextran sulfate sodium-induced murine colitis activates NF-?B and increases galanin-1 receptor expression.  Am J Physiol 2000; 278: G797-G810.

Matkowskyj KA, Schonfeld, D, Benya RV.  Quantitative immunohistochemistry by measuring cumulative signal strength using commercially available software Photoshop and Matlab.  J Histochem Cytochem 2000; 48: 303-311.

Hecht G, Marrero JA, Danilkovich A, Matkowskyj KA, Savkovic SD, Koutsouris A, Benya RV.  Pathogenic Escherichia coli increase Cl- secretion from intestinal epithelial by up-regulating galanin-1 receptor expression.  J Clin Invest 1999; 104: 253-262.

Matkowskyj KA, Marrero JA, Carroll RE, Green R, Benya RV.  Azoxymethane-induced fulminant hepatic failure in mice: characterization of a new animal model.  Am J Physiol 1999; 277: G455-G462.

Matkowskyj KA, Carroll RE, Chakrabarti S, McDonald T, Benya RV.  Aberrant expression of gastrin-releasing peptide and its receptor by well differentiated colon cancers in humans.  Am J Physiol 1999; 276: G655-G665.

Benya RV, Matkowskyj KA, Danilkovich A, Hecht G.  Galanin causes Cl- secretion in the human colon.  Potential significance of inflammation-associated NF-?B activation on galanin-1 receptor expression and function. Ann NY Acad Sci USA 1998; 869: 64-77.

Marrero JA, Ostrovskiy DA, Matkowskyj KA, Koutsouris A, Hecht G, Benya RV.  Electrophysiological characterization of human distal colon.  Description of a novel technique for isolating gastrointestinal epithelium. Dig Dis Sci 1998; 43: 2439-2445.

Lorimer DD, Matkowskyj KA, Benya RV.  Cloning, chromosomal localization, and transcriptional regulation of the human galanin-1 receptor gene (GALN1R). Biochem Biophys Res Comm 1997; 241: 558-564.

CHAPTERS:
Handbook of Immunochemistry and in situ Hybridization of Human Carcinomas.  Volume 4:  Molecular Genetics, Gastrointestinal Carcinomas, and Ovarian Carcinomas.  Quantitative Immunohistochemistry (Q-IHC) Determining the Norm of the Image Data File.  Authors:  Kristina A. Matkowskyj, PhD, Randal Cox, PhD, Richard V. Benya, MD.  Volume 4, p. 279. 

Joshua Meeks, MD, PhD (PGY3), Department of Urology

Information not yet available

David Montgomery, MD, PhD (PGY3), Department of Medicine Education: B.S., Morehouse College, Biology, 1996 Ph.D., University of Illinois,Physiology & Biophysics, 2001 M.D., Northwestern University, 2005

Research Interests:

My previous work sought to enlarge our understanding of the role of the cardiac troponin regulatory complex in physiologic myocardial function (with Dr. R. John Solaro), in hypertrophic and dilated cardiomyopathies, as well as in the eventual progression to end-stage pump failure (with Dr. Peter M. Buttrick). 

Now, my research interests have been broadened to include investigation of the cardiovascular system as a whole, with particular focus on translational questions.  Under the tutelage of Dr. Douglas Vaughan, I will study the role of the plasminogen activator inhibitor (PAI-1), a key regulator of the fibrinolytic system, and its role in ischemic cardiovascular disease.  In particular, I plan to contribute to our understanding of how PAI-1 modulates the vascular and myocardial housekeeping processes (i.e., myocardial scar formation) that occur after ischemic injury.

My overall goal for training in cardiology is to merge my clinical and research interests.  To this end, I will focus my clinical cardiology fellowship on the cardiac patient with atherosclerotic coronary and peripheral artery disease.  As a clinical cardiologist, I will specialize in percutaneous, as well as novel medical approaches to this common disease entity. 

Ultimately, my career goal is to help advance our state of thinking on critical issues in cardiovascular medicine through innovative patient care and translational research.      

Publications:

ARTICLES:

Montgomery DE, Rundell VLM, Goldspink PH, Urboniene D, Geenen DL, de Tombe PP, Buttrick PM.  PKC* induces systolic cardiac failure marked by exhausted inotropic reserve and intact Frank-Starling mechanism.  Am. J. Physiol: Heart and Circ.  289 (5): H1881-8, 2005. 

Goldspink PH., Montgomery DE., Walker LA, McKinney RD, Ping P., Geenen DL., Solaro RJ and Buttrick PM. Protein Kinase C* over-expression alters the cardiac myofilament properties and composition during the progression to heart failure. Circ Res. 95: 424-432, 2004.

Solaro RJ, Montgomery D, Wang L, Burkart EM, Ke Y, Vahebi S, Buttrick PM.  Integration of Pathways that Signal Cardiac Growth with Modulation of Myofilament Activity.  J. Nuclear Cardiol.  9: (5): 523-33, 2002.

Montgomery DE, Wolska BM, Pyle WG, Roman BB, Dowell JC, Buttrick PM, Koretsky AP, del Nido PJ and Solaro RJ. Altered *-Adrenergic Response and Myofilament Activation in Mouse Hearts Lacking Troponin I Phosphorylation Sites.  Am J. Physiol: Heart and Circ., 282 (6):  H2397-2405, 2002.

Montgomery DE, Tardiff JC and Chandra M.  Cardiac Troponin T Mutations: correlation between the type of mutation and the nature of myofilament dysfunction.  Journal of Physiology (London), 536 (2):  583-592, 2001.
 
Montgomery DE, Chandra M, Huang QQ, Jin JP and Solaro RJ. Transgenic Incorporation of Skeletal TnT into Cardiac Myofilaments Blunts PKC-mediated Depression of Force. Am J. Physiol: Heart and Circ., 280 (3): H1011-H1018, 2001.

Huang L, Wolska BM, Montgomery DE, Burkart EM, Buttrick PM, and Solaro RJ. Increased contractility and altered calcium transients of myocytes from transgenic mouse hearts conditionally expressing PKCβ.  Am J. Physiol: Cell, 280 (5): C1114-C1120, 2001.

Chandra M, Montgomery DE, Kim JF, and Solaro RJ.  The N-terminal Region of Troponin T Is Essential for Maximal Activation of Rat Cardiac Myofilaments.  Journal of Mol. Cell. Cardiol. 31 (4): 867-880, 1999.

Donald CD, Montgomery DE, Emmett N, and Cooke DB. Invasive Potential and Substrate Dependence of Attachment in the Dunning R-3327 Rat Prostate Adenocarcinoma Model. Invasion and Metastasis 18 (4): 165-175, 1998/99.

Golspink PH, Montgomery DE, Ruch, Buttrick PM, Garcia J.  The effect of PKCβ  overexpression on calcium transients: an isoform-specific physiologic role. In preparation

Goldspink PH, Montgomery DE, Geenen DL, Buttrick PM.  Aortic banding precipitates end-stage dilated cardiomyopathy in PKC? overexpressing mice.  In preparation

ABSTRACTS:

Posters or Oral Presentations at National Meetings

Montgomery DE, Goldspink PH and Buttrick PM. Diminished Systolic Function and Inotropic Reserve in Mice Hearts Over-expressing PKC*:  a P-V loop analysis. NHLBI Conference (Chicago, IL), November 2002.

Montgomery DE, Tardiff J, Chandra M.  Cardiac Troponin T Mutations:  The Correlation between the Type of Mutation and the Nature of Myofilament Dysfunction. Biophys. J. 79 (1):  A381, 2001.

Goldspink PH, Montgomery DE, Ping P, Geenen DL, Solaro RJ and Buttrick PM. Cardiac Expression of PKC* Alters the Activity of the Myofilaments and Increases Fetal Gene Expression Before the Onset of Cardiac Hypertrophy. Circulation Suppl. 102, (18): Il-159, 2000.

Roman BB, Montgomery DE, Koretsky AP, del Nido PJ, Solaro RJ and Buttrick PM. Targeted Mutation of Protein Kinase C Phosphorylation Sites on Cardiac Troponin I (TnI) Alters Cardiac Function in vivo.  Circulation Suppl. 102 (18):  Il-160, 2000.

Montgomery DE, Koretsky AP, del Nido PJ, Cowan DB, Roman BB, Leiden JM and Solaro RJ.  Hierarchy of Functional Significance for PKC-specific Sites on Cardiac Troponin I. Biophys. J. 78 (1): A365, 2000.

Montgomery DE, Chandra M, Huang QQ, Jin JP, Solaro RJ.  Transgenic incorporation of chicken fast skeletal TnT into cardiac myofilaments blunts the PKC-induced depression of maximal tension. Circulation Suppl.. 100 (18):  I-121, 1999.

Chandra M, Montgomery DE, Solaro RJ.  N-terminal truncation of rat cardiac troponin T decreases maximal ATPase activity of cardiac myofilaments.  Biophys. J. 74: A52, 1998.

R. Kannan Mutharasan, MD (PGY5), Department of Medicine

Education:

B.S., Northwestern University, Biomedical Engineering, 1999
M.D., Northwestern University, 2003

Research Interests:

I am interested most in understanding the mechanisms that lead to heart failure so that we can undo the process. That heart failure is so prevalent makes it an important problem. That it is becoming more prevalent makes it an urgent one. This all appeals to the clinician in me. The scientist in me is fascinated by the complexity of the biology—a failing heart evokes hypertrophy, fibrosis, apoptosis, and myriad other events we have only begun to piece together. How does the heart fail, and how much of that failure can we undo so that our patients may live long, healthy lives? These are the types of questions I want to spend my career investigating.

The nice thing about the PSTP is that it is so flexible. I am finishing my clinical training first because I think such exposure will help me formulate better research questions. But those that want to interpose research training between residency and clinical fellowship are welcome to. However you do things and whatever your interest, I am sure you will find Northwestern to be a great place to learn, train, work, and—most fun of all—discover.

Kobayashi M. Mutharasan RK. Feng J. Roberts MF. Lomasney JW. Identification of hydrophobic interactions between proteins and lipids: free fatty acids activate phospholipase C delta1 via allosterism. Biochemistry. 43(23):7522-33, 2004 Jun 15.

Egon Ozer, MD, PhD (PGY2), Department of Medicine

Education:

B.S., St. Cloud State University, Biotechnology, 2000
M.D./Ph.D., University of Iowa, Molecular Biology, 2006

Research Interests:

I conducted my graduate research in the laboratory of Dr Joseph Zabner, MD.  The primary focus of my research was the prevention of Pseudomonas aeruginosa biofilm formation in the lungs of cystic fibrosis patients.  I directed my efforts at blocking Pseudomonas quorum sensing, a process whereby Pseudomonas and other bacteria regulate their gene expression in response to chemical signaling molecules, acyl-homoserine lactones secreted and detected by the bacteria.  In P. aeruginosa, quorum sensing controls the expression of genes necessary for effective biofilm formation.  Pseudomonas biofilms are colonies of bacteria within a self-secreted polysaccharide matrix that are highly resistant to biocides and antibiotics.  Pseudomonas biofilms are medically relevant as they are shown to form in the lungs of cystic fibrosis patients and contribute to significant morbidity and mortality in this population.  My hypothesis was that degradation of P. aeruginosa acyl-homoserine lactones by mammalian tissues would interrupt quorum sensing and prevent biofilm formation.  During my research I discovered that human airway epithelia and other mammalian tissues possess an innate ability to degrade acyl-homoserine lactones.  I further characterized this as an enzymatic activity and traced the activity to a family of proteins, the paraoxonases.  I further found that mammalian paraoxonase activity was both necessary and sufficient to both degrade quorum sensing molecules as well as prevent Pseudomonas biofilm formation and that common polymorphisms within one member of this family, paraoxonase 2, had significant effects on the ability of the enzyme to block quorum sensing.  My future research goals include further study into interactions between hosts and pathogens, as well as molecular mechanisms by which humans are able to protect themselves from infection.

Publications:

Stoltz DA, Ozer EA, Ng CJ, Yu J, Reddy ST, Lusis AJ, Bourquard N, Parsek MR, Zabner J, Shih DM. Paraoxonase-2 Deficiency Enhances Pseudomonas aeruginosa Quorum Sensing in Murine Tracheal Epithelia,  Am J Physiol Lung Cell Mol Physiol. 2006 Nov 22. Epub ahead of print

Ozer EA, Pezzulo A, Shih DM, Chun C, Furlong C, Lusis AJ, Greenberg EP, Zabner J. Human and murine paraoxonase 1 are host modulators of Pseudomonas aeruginosa quorum-sensing.  FEMS Microbiol Lett. 2005 Dec 1;253(1):29-37.

Brown CL, Graham SM, Cable BB, Ozer EA, Taft PJ, Zabner J. Xylitol enhances bacterial killing in the rabbit maxillary sinus.  Laryngoscope. 2004 Nov;114(11):2021-4.

Chun CK, Ozer EA, Welsh MJ, Zabner J, Greenberg EP. Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway epithelia.  Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3587-90.

Daniel Popowich, MD (PGY5), Department of Surgery

Education:

B.S., Emory University for College, Anthropology and Human Biology
M.D., Jefferson Medical College

Research Interests:

Our lab’s main area of research is in nitric oxide and its ability to decrease the neointimal hyperplasia that ensues following vascular surgical procedures leading to re-stenosis. Specifically I am looking into the mechanism by which nitric oxide causes vascular smooth muscle cell (VSMC) apoptosis using a p53 knockout model.  This apoptosis appears to be mediated via NO-induced increase in reactive oxygen species.  Contrary to the currently accepted paradigm of p53 as a pro-apoptotic signal, it appears that in this model the presence of p53 protects VSMC from apoptosis.

I am also working to develop a spontaneous nitric oxide-releasing prosthetic bypass grafts in collaboration with the Biomedical Engineering department that we will evaluate in a porcine model of vascular bypass grafting.  The obvious goal of this project is to attempt to engineer improved vascular conduits that would afford increased patency and longevity over the currently available models.