Pathology Research Brochure

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Division of Cardiovascular Pathology

Email csteenb1@jhmi.edu

Phone (410) 502-5982

Charles J. Steenbergen, M.D., Ph.D.
Primary Appointment in Pathology

My research is on mechanisms of ischemic heart disease, and in particular, endogenous mechanisms that can be activated to protect the heart during a subsequent episode of ischemia and reperfusion. I am interested in identifying signal transduction pathways that are involved in cardioprotection, and understanding how these signaling pathways confer their protective effect. We have been interested in mechanisms of injury involving ionic dysequilibrium, and have used magnetic resonance spectroscopic techniques to monitor ion concentrations in intact hearts during ischemia and reperfusion. Since infarct size is a major determinant of clinical outcome in patients with ischemic heart disease, we hope that better understanding of these protective mechanisms will lead to the development of better therapies for patients with coronary artery disease and patients undergoing heart surgery.

Publications

Tong, H., Bernstein, D., Murphy, E, Steenbergen, C.: The role of beta-adrenergic receptor signaling in cardioprotection. FASEB J. 2005; 19: 983-985.
Hanlon, P.R., Arcasoy, M.O., Fu, P., Wright, G.L., Steenbergen, C., Murphy, E.: Mechanisms of erythropoietin-mediated cardioprotection during ischemia-reperfusion injury: role of protein kinase C signaling. FASEB J. 2005; 19: 1323-1325.
Murphy, E. and Steenbergen, C.: Inhibition of GSK-3beta as a target for cardioprotection: the importance of timing, location, duration and degree of inhibition. Expert Opin. Ther. Targets 2005; 9: 447-456.
Murphy, E., Imahashi, K, Steenbergen, C.: Bcl-2 regulation of mitochondrial energetics. Trends in Cardiovasc. Med. 2005; 15: 297-302.
Murphy, E. and Steenbergen, C.: Preconditioning: the mitochondrial connection. Ann. Rev. Physiol. 2007, in press.

Email	mhalush1@jhmi.edu
Phone	(410) 614-8138

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Marc K. Halushka, M.D., Ph.D.

Primary Appointment in Pathology

Vascular disease is the primary cause of morbidity and mortality among diabetics. My laboratory is investigating the role of advanced glycation end products (AGEs) on endothelial dysfunction. We are primarily working with human coronary and aortic endothelial cells in vitro to establish the role of AGEs on endothelial-mesenchymal transdifferentiation (EndoMT). We are also developing an animal model to study the role of AGEs on EndoMT.

Publications

Halushka MK, Selvin E, Lu J, Macgregor AM, Cornish TC. The Use of Human Vascular Tissue Microarrays for Measurement of Advanced Glycation End Products. J Histochem Cytochem. 2009 Feb 16.
Halushka MK, Cornish TC, Lu J, Selvin S, Selvin E. Creation, validation, and quantitative analysis of protein expression in vascular tissue microarrays. Cardiovasc Pathol. 2009 Feb 10
Maleszewski JJ, Miller DV, Lu J, Dietz HC, Halushka MK. Histopathologic findings in ascending aortas from individuals with Loeys-Dietz syndrome (LDS). Am J Surg Pathol. 33(2):194-201, 2009.
Maleszewski J, Lu J, Fox-Talbot K, Halushka MK. Robust immunohistochemical staining of several classes of proteins in tissues subjected to autolysis. J Histochem Cytochem. 55(6):597-606, 2007.
Halushka MK, Walker LP, Halushka PV. Genetic variation in cyclooxygenase 1: effects on response to aspirin. Clin Pharmacol Ther. Jan;73(1):122-30, 2003.
Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A. Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet. Jul;22(3):239-47, 1999.

Email	ghutchi@jhmi.edu
Phone	(410) 955-3765
Related Websites
Division of Cardiovascular Pathology

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Grover M. Hutchins, M.D.

Interim Director, Division of Cardiovascular Pathology
Primary Appointment in Pathology; Secondary Appointment in Art as Applied to Medicine
Member, Graduate Program in Medical and Biological Illustration

My investigations are primarily on the pathogenesis of various abnormalities based on study of patients at autopsy. Particular interests are in cardiovascular, pulmonary, and pediatric pathology. The studies are generally conducted by review of the appropriate clinical and pathologic features of the cases.

Publications

Volmar, Keith E., Fritsch, Michael K., Perlman, Elizabeth J. and Hutchins, Grover M.: Patterns of congenital lower urinary tract obstructive uropathy:Relation to abnormal prostate and bladder development and the prune bellysyndrome. Pediatr Dev Pathol 4:467-472, 2001.
Volmar, Keith E. and Hutchins, Grover M. Aortic and mitralfenfluramine-phentermine valvulopathy in 64 patients treated with anorecticagents. Arch Pathol Lab Med 125:1555-1561, 2001.
Haderer, Joanne M., Pannu, Harpreet K. Genadry, Rene, Hutchins, GroverM. Controversies in female urethral anatomy and their significance for understanding urinary continence: observations and literature review. Int Urogynecol J Pelvic Floor Dysfunct 13:236-252,2002
Rogers, Daniel S., Paidas, Charles N., Morreale, Robert F., Hutchins,Grover M. Septation of the anorectal and genitourinary tracts in the human embryo: Crucial role of the catenoidal shape of the urorectal sulcus.Teratology 66:144-152,2002

Email	eratovi1@jhmi.edu
Phone	(410) 955-2992

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Edward A. Ratovitski, Ph.D.

Primary Appointment in Dermatology; Secondary Appointments in Pathology, Medicine, Otolaryngology-Head and Neck Surgery
Member, Graduate Program in Biochemistry, Cellular and Molecular Biology

My research focuses on signal transduction mechanisms involved in regulation of NOS2 and p63 during embryonic development, tumorigenesis and inflammation. By studying the protein-protein interactions of NOS2, I have identified novel mechanisms allowing to control NOS2 dimerization and, therefore its activity in macrophages. I am also interested in understanding the role of p53 homologue p63 in cancer and development. I have discovered that p63 isoform lacking the transactivation domain (delta-Np63) has particularly high impact on tumorigenesis acting as a putative oncoprotein and is involved in many signaling pathways. P53 binds to delta-NP63 and targets it into a caspase-dependent degradation pathway. However, when p53 mutations occur in cancer, delta-Np63 accumulates and positively regulates beta-catenin signaling leading to activation of genes involved in cell proliferation. I am also interested in the study of midkine signaling in tumorigenesis. Midkine is a heparin-binding growth factor activating JAK/Stat signaling pathway that induces tumorigenic phenotype.

Publications

Ratovitski E, Quick RA, McMillan A, Bao C, Kozlovsky C, Lowenstein CJ: Nitric-oxide Synthase-2 (NOS-2)-associated Protein Expressed in Macrophages Inhibits NOS2 Activity and Prevents NOS2 Homodimerization. J Biol Chem 274:30250-30259, 1999.
Ratovitski E, Patturajan M, Hibi K, Yamaguchi K, Trink B, Sidransky D: P53 associates with and targets deltaNp63 into a protein degradation pathway. Proc Natl Acad Sci USA 98:1817-1822, 2001.
Patturajan M, Nomoto S, Sommer M, Fomenkov A, Hibi K, Zangen R, Poliak N, Califano J, Trink B, Ratovitski E, Sidransky D.DeltaNp63 induces beta-catenin nuclear accumulation and signaling. Cancer Cell. 1:369-379, 2002.
Fomenkov A, Huang YP, Topaloglu O, Brechman A, Osada M, Fomenkova T, Yuriditsky E, Trink B, Sidransky D, Ratovitski E. P63 alpha mutations lead to aberrant splicing of keratinocyte growth factor receptor in the Hay-Wells syndrome. J Biol Chem. 278:23906-23914, 2003.