PSTP Participants

Andrew Gawron (PGY 2)

BS: Truman State University, Chemistry (1996)
PhD: University of Kansas, Pharmaceutical Chemistry (2001)
MD: Northwestern University (2007)
Subspecialty Interest(s): Gastroenterology, Hepatology, Hematology/Oncology

Publications

  • Kohlgraf KG. Gawron AJ. Higashi M. VanLith ML. Shen X. Caffrey TC. Anderson JM. Hollingsworth MA. Tumor-specific immunity in MUC1.Tg mice induced by immunization with peptide vaccines from the cytoplasmic tail of CD227 (MUC1). Cancer Immunology, Immunotherapy. 53(12):1068-84, 2004 Dec.
  • Kohlgraf KG. Gawron AJ. Higashi M. Meza JL. Burdick MD. Kitajima S. Kelly DL. Caffrey TC. Hollingsworth MA. Contribution of the MUC1 tandem repeat and cytoplasmic tail to invasive and metastatic properties of a pancreatic cancer cell line. Cancer Research. 63(16):5011-20, 2003 Aug 15.
  • Gawron AJ. Martin RS. Lunte SM. Microchip electrophoretic separation systems for biomedical and pharmaceutical analysis. European Journal of Pharmaceutical Sciences. 14(1):1-12, 2001 Aug.
  • Gawron AJ. Martin RS. Lunte SM. Fabrication and evaluation of a carbon-based dual-electrode detector for poly(dimethylsiloxane) electrophoresis chips. Electrophoresis. 22(2):242-8, 2001 Jan.
  • Martin RS. Gawron AJ. Fogarty BA. Regan FB. Dempsey E. Lunte SM. Carbon paste-based electrochemical detectors for microchip capillary electrophoresis/electrochemistry. Analyst. 126(3):277-80, 2001 Mar.
  • Gawron AJ. Lunte SM. Detection of neuropeptides using on-capillary copper complexation and capillary electrophoresis with electrochemical detection. Electrophoresis. 21(15):3205-11, 2000 Sep.
  • Martin RS. Gawron AJ. Lunte SM. Dual-electrode electrochemical detection for poly(dimethylsiloxane)-fabricated capillary electrophoresis microchips. Analytical Chemistry. 72(14):3196-202, 2000 Jul 15.
  • Gawron AJ. Lunte SM. Optimization of the conditions for biuret complex formation for the determination of peptides by capillary electrophoresis with ultraviolet detection. Electrophoresis. 21(10):2067-73, 2000 Jun.

Wenyu Huang (PGY 2)

PhD: Northwestern University, Nueroscience (2007)
MD: Beijing Medical University (1998)
Subspecialty Interest(s): Endocrinology

Publications

  • Huang W, Acosta-Martinez M, Levine JE. 2008 Ovarian steroids stimulate adenosine triphosphate-sensitive potassium (KATP) channel subunit gene expression and confer responsiveness of the gonadotropin-releasing hormone pulse generator to KATP channel modulation.  Endocrinology 149(5):2423-32.

  • 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.

Shawn Rose (PGY 2)

BS: University of Miami, Psychology (1999)
PhD: University of Miami, Immunology (2005)
MD: University of Miami (2007)
Subspecialty Interest(s): Rheumatology

Publications

  • Rose S. Lichtenheld M. Foote MR. Adkins B. Murine neonatal CD4+ cells are poised for rapid Th2 effector-like function. Journal of Immunology. 178(5):2667-78, 2007 Mar 1.
  • Rose S. Guevara P. Farach S. Adkins B. The key regulators of adult T helper cell responses, STAT6 and T-bet, are established in early life in mice. European Journal of Immunology. 36(5):1241-53, 2006 May.

Egon Ozer (PGY 3)

BS: St. Cloud State University, Biotechnology (2000)
PHD: University of Iowa, Molecular Biology (2006)
MD: University of Iowa (2007)
Subspecialty Interest(s): Infectious Diseases

I conducted my graduate research in the laboratory of Dr Joseph Zabner, MD at the University of Iowa.  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 in 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 JM. Reddy ST. Lusis AJ. Bourquard N. Parsek MR. Zabner J. Shih DM. Paraoxonase-2 deficiency enhances Pseudomonas aeruginosa quorum sensing in murine tracheal epithelia. American Journal of Physiology - Lung Cellular & Molecular Physiology. 292(4):L852-60, 2007 Apr.
  • 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 Microbiology Letters. 253(1):29-37, 2005 Dec 1.
  • Brown CL. Graham SM. Cable BB. Ozer EA. Taft PJ. Zabner J. Xylitol enhances bacterial killing in the rabbit maxillary sinus. Laryngoscope. 114(11):2021-4, 2004 Nov.
  • Chun CK. Ozer EA. Welsh MJ. Zabner J. Greenberg EP. Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway epithelia.[see comment]. Proceedings of the National Academy of Sciences of the United States of America. 101(10):3587-90, 2004 Mar 9.

Brian Layden (PGY 4)

BS: Loyola University (Chicago), Psychology (1997)
PhD: Loyola University (Chicago), Chemistry (2001)
MD: University of Illinois at Chicago (2005)
Subspecialty Interes(s): Endocrinology

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.

David Montgomery (PGY 4)

BS: Morehouse College, Biology (1996)
PhD: University of Illinois at Chicago, Physiology & Biophysics (2001)
MD: Northwestern University (2005)
Subspecialty Interes(s): Cardiology

My previous research sought to enlarge our understanding of the role of cardiac thin filament proteins, specifically the troponin regulatory complex, in physiologic, beat-to-beat ventricular function; the myofilament contributions to hypertrophic cardiomyopathy; and most recently, the importance of troponin signaling in the progression of cardiac failure.  Clinically, I plan to focus on cardiovascular disease and more definitive approaches to the problems facing the cardiac patient.  My ultimate career goal is to help advance our state of thinking on critical issues in cardiovascular medicine through translational research and innovative patient care.  In the intervening time, more specific clinical and research interests are evolving.

Publications

  • Montgomery DE. Rundell VL. Goldspink PH. Urboniene D. Geenen DL. de Tombe PP. Buttrick PM. Protein kinase C epsilon induces systolic cardiac failure marked by exhausted inotropic reserve and intact Frank-Starling mechanism. American Journal of Physiology - Heart & Circulatory Physiology. 289(5):H1881-8, 2005 Nov.
  • Goldspink PH. Montgomery DE. Walker LA. Urboniene D. McKinney RD. Geenen DL. Solaro RJ. Buttrick PM. Protein kinase Cepsilon overexpression alters myofilament properties and composition during the progression of heart failure. Circulation Research. 95(4):424-32, 2004 Aug 20.
  • Huang L. Wolska BM. Montgomery DE. Burkart EM. Buttrick PM. Solaro RJ. Increased contractility and altered Ca(2+) transients of mouse heart myocytes conditionally expressing PKCbeta. American Journal of Physiology - Cell Physiology. 280(5):C1114-20, 2001 May.
  • Montgomery DE. Wolska BM. Pyle WG. Roman BB. Dowell JC. Buttrick PM. Koretsky AP. Del Nido P. Solaro RJ. alpha-Adrenergic response and myofilament activity in mouse hearts lacking PKC phosphorylation sites on cardiac TnI. [American Journal of Physiology - Heart & Circulatory Physiology. 282(6):H2397-405, 2002 Jun.
  • Montgomery DE. Tardiff JC. Chandra M. Cardiac troponin T mutations: correlation between the type of mutation and the nature of myofilament dysfunction in transgenic mice. Journal of Physiology. 536(Pt 2):583-92, 2001 Oct 15.
  • Montgomery DE. Chandra M. Huang Q. Jin J. Solaro RJ. Transgenic incorporation of skeletal TnT into cardiac myofilaments blunts PKC-mediated depression of force. American Journal of Physiology - Heart & Circulatory Physiology. 280(3):H1011-8, 2001 Mar.
  • Chandra M. Montgomery DE. Kim JJ. Solaro RJ. The N-terminal region of troponin T is essential for the maximal activation of rat cardiac myofilaments. Journal of Molecular & Cellular Cardiology. 31(4):867-80, 1999 Apr.
  • Donald CD. Montgomery DE. Emmett N. Cooke DB 3rd. Invasive potential and substrate dependence of attachment in the dunning R-3327 rat prostate adenocarcinoma model. Invasion & Metastasis. 18(4):165-75, 1998-99.

Michael Burke (PGY 5)

BS: Villanova University, Comprehensive (1999)
MD: Thomas Jefferson University (2004)
Subspecialty Interest(s): Cardiology

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.

Published Abstracts

  • Burke MA and JE Knepper. Cathepsin L is differentially upregulated during involution of the mouse mammary gland. Proceedings of the 91st annual meeting of the American Association for Cancer Research, San Francisco, CA, April 1-5; vol 41, March 2000.
  • Burke MA, Reshamwala R, and JE Knepper. Cathepsin L is an Active Participant in Mammary Gland Involution in the Mouse. Proceedings of the 92nd annual meeting of the American Association for Cancer Research, New Orleans, LA, March 24-28; vol 42, March 2001.
  • Burke MA, and H Ardehali. Snf1-related kinase (SNRK) is upregulated in ischemic tissue, and its overexpression increases cell death. Circ Res. 2007; 101:E61.
  • Gordon L, Singh A, Prachand S, Lieberman E, Sun L, Burke MA, Naik TJ, Prasad S, and H Ardehali. ErbB2 blockade and downregulation lead to cardiomyocyte cell death through distinct pathways.  Circ Res. 2007; 101:E62.

Publications

  • Burke MA, Hutter D, Reshamwala RP, and JE Knepper. Cathepsin L plays an active role in involution of the mouse mammary gland. Developmental Dynamics. 2003; 227:315-22.
  • Burke MA and WG Cotts. Interpretation of B-type natriuretic peptide in cardiac disease and other comorbid conditions. Heart Fail Rev. 2007; 12:23-36.
  • Burke MA and H Ardehali. 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.


Nils Johnson (PGY 5)

BS: University of British Columbia, Physics and Computer Science (2000)
MD: Columbia University (2004)
Subspecialty Interest(s): Cardiology

My major research focus is diseases of the coronary arteries. The most common of these, atherosclerosis, manifests itself most clearly through abnormal myocardial perfusion. I study perfusion using both noninvasive and invasive techniques, from PET and cardiac MRI to coronary pressure-flow wires. Overall I enjoy applying my background in physics, mathematics, and computer science to medical problems. In addition, I am enrolled in the Master of Science in Clinical Investigation (MSCI) degree program here at Northwestern.

Publications

  • Johnson NP, Wu E, Bonow RO, Holly TA. Relation of exercise capacity and body mass index to mortality in patients with intermediate-to-high risk for coronary artery disease. American Journal of Cardiology, October 2008 (in press).
  • Johnson NP, Denes P. 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, 2007 July.
  • 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 subjects. Journal of Nuclear Medicine. 46(9):1427-37, 2005 Sep.
  • Johnson NP. Advantages to transforming the receiver operating characteristic (ROC) curve into likelihood ratio co-ordinates. Statistics in Medicine. 23(14):2257-66, 2004 Jul 30. 
  • Johnson NP. The Brachistochrone Problem. College Mathematics Journal. 35(3):192-197; 2004 May.

R. Kannan Mutharasan (PGY 6)

BS: Northwestern University, Biomedical Engineering (1999)
MD: Northwestern University (2003)
Subspecialty Interest(s): Cardiology

I am a PGY-5, and am in the third year of my Cardiology fellowship. Except for the year I spent in London studying British history, this marks my 12th year at Northwestern. I absolutely love it here.

My long-term research goal is to better understand the mechanisms that lead to heart failure.  Heart failure's prevalence makes it an important problem; its growing prevalence 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 "big picture" questions I want to spend my career investigating.

I am very excited to be joining Dr. Hossein Ardehali's lab this summer.  Our first interaction occurred when I was a first-year fellow on-call in the CCU.  I was managing an ST-elevation MI patient in cardiogenic shock.  He was a great mentor in the management of that patient that night, and has offered me continued guidance over the last few years.  I plan on working on a series of projects to examine the roles microRNA play in apoptosis of cardiomyocytes.

The nice thing about the PSTP is that it is so flexible. I elected to complete my clinical training first because I believed this would lead me to formulate more incisive research questions in the lab.  But those who wish 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.

Publications

  • Mutharasan RK. Nagaraj A. Hamilton AJ. McPherson DD. Bharati S. Computer three-dimensional reconstruction of the atrioventricular conduction system. Pacing & Clinical Electrophysiology. 27(6 Pt 1):740-8, 2004 Jun.
  • 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.