Suzanne K. Murphy PhD
Suzanne K. Murphy PhD
Dean of Misher College of Arts & Sciences
Director of Pre-Health Professions Programs
Professor of Biology
Post-Doctoral Fellowship (SmithKline and French Laboratories Corp.Department of Tumor Biology )
Post-Doctoral Fellowship (Albert Einstein Medical Center Department of Pediatrics )
Heat shock proteins (HSP) are an evolutionarily conserved group of proteins that play a pivotal role in maintaining cell viability in response to stress. Our lab in interested in how these ubiquitously expressed HSPs can have both beneficial and deleterious effects by promoting normal physiological processes as well as disease states such as cancer.
Heat shock proteins (HSP) are an evolutionarily conserved group of proteins that play a vital role in maintaining cell viability in response to stress. Their ability to catalyze the proper folding of misfolded proteins and impair apoptosis help protect cells from a variety of stressors. For this reason, our lab is interested in how these ubiquitously expressed HSPs can have both beneficial and detrimental effects by promoting normal physiological processes as well as disease states such as cancer.
HSP involvement in renal tolerance of osmotic stress
Previous work in our lab has focused on understanding how medullary cells of the kidney function in an environment of severe osmotic stress. Renal medullary cells normally exist in a hypertonic environment and can tolerate acute osmotic stress at 830 mOsm. Following RNAi mediated knock down of HSP-70 we observed at least a 50% reduction in the viability of medullary cells subjected to acute osmotic stress, suggesting a role for HSP70 in osmotic stress tolerance. Further work has focused on the role of HSP-70 and other HSPs in the adaptation of medullary cells to osmotic stress.
Osmotic stress and cytoskeletal rearrangement in hematopoietic stem cells
Another earlier project in our lab focused on the effects of osmotic stress on the cytoskeletal arrangement of human hematopoietic (KG1a) cells. We found that in response to hypertonic stress KG1a cells extrude filopodia. The lab also analyzed p38MAPk and heat shock protein-27 (HSP-27) regulation of hypertonic stress induced filopodia formation in KG1a cells.
HSP involvement in cancer progression
More currently, the lab has focused on the role HSPs play in cancer progression. Cancer cells are under a constant state of stress due to aberrant metabolism, chaotic signal transduction, and exposure to chemotherapeutic agents. As a result, cancer cells become dependent on proteins such as HSPs for viability, resistance to chemotherapy, and to escape anoikis in order to metastasize. Therefore, it is no surprise clinical studies have shown increased expression of HSPs correlates with poor prognosis.
One of our current projects is focused on elucidating the role of HSPs in bestowing resistance to chemotherapeutic agents in Ras transformed lung carcinomas. Our preliminary findings have shown that cancer cells with the ability to survive exposure to the chemotherapeutic agent cisplatin have an increased expression of HSP-27 phosphorylated at serine 82. Work is in progress to determine the effects that phosphorylated HSP-27 has on impairing apoptosis in these chemoresistant cells.
Another cancer related project in the lab is focused on the role HSPs play in helping Ras transformed lung carcinomas escape anoikis, which is crucial for the ability of cancer cells to metastasize. Our preliminary findings have shown a dramatic increase in the expression of HSP-70 in these cells when grown in suspension. Work is underway to determine if the anti-apoptotic properties of HSP-70 are involved in helping lung carcinomas survive in suspension and escape anoikis.
Selected Scholarly Activity
(* indicates undergraduate student)
(** indicates graduate student)
Jack Carter and Suzanne K. Murphy “Heat shock transcription factor-1 and heat shock protein60 are important for lung carcinoma anoikis resistance” Proceedings of the American Association for Cancer Research,2014 (in press)
Patrick Flynn, Jessica Byerly**, Tracy Berner*, Suzanne K. Murphy “Caspase 8 cleavage is inhibited downstream of p38 MAPK in cisplatin resistant cells” Molecular Biology of the Cell. 22, 1904 (2011).
H. Tyagi, J. Byerly**, J. Carter*, S. Merchant*, M.R. Kasschau and S.K. Murphy. “Osmotic stress response of kidney cells following the RNAi mediated knock-down of hsp70” Molecular Biology of the Cell. 21, 2395 (2010).
Jack Carter*, Priyanka Patel**, Mahasweta Dutt**, Himani Tyagi, Jessica Byerly**, Margaret Kasschau,and Suzanne K Murphy ”Hypertonic Stress Induced Filopodia Formation is Regulated by p38MAPk and hsp27 in Human Acute Myelogenous Leukemic Cell Line Kg1a” Molecular Biology of the Cell. 21, 1134 (2010).
P. Patel**, H. Tyagi, J. Carter*, M. Dutt**, M. R. Kasschau and S. K. Murphy. “Filopodia formation on exposure to hypertonic stress is regulated by hsp27 and p38 MAPK in acute myelogenous leukemic cell line Kg1a.” Molecular Biology of the Cell. 20,1117 (2009).
P. Patel, H. Tyagi, A. Khanna, M. Kasschau and S. Murphy. “Role of P38MAPK and heat shock proteins, HSP27 and HSP70, in Osmotic Stress in Renal vs. Blood Cells: A Comparative Study.” Molecular Biology of the Cell,19, 0361 (2008).
P. Patel, M. Dutt, M.R. Kasschau and S.K. Murphy. “Effect of P38MAPK on Filopodial Formation in KGla Human Hemotopoietic Cell Line.” Molecular Biology of the Cell, 18, 169 (2007).
Formation in a Human Hematopoietic Cell Line under Hypertonic Stress.” Molecular Biology of the Cell, 17, 2361 (2006)
A. Khanna, M.R. Kasschau and S.K. Murphy. “Cytoskeletal Reorganization in a Kidney Cell Line (LLC-PK1) under Hypertonic Stress.” Molecular Biology of the Cell, 17, 2361 (2006).
P. Patel, H. Tyagi, A. Khanna, M. Kasschau and S. Murphy. “Role of P38MAPK and heat shock proteins, HSP27 and HSP70, in Osmotic Stress in Renal vs. Blood Cells: A Comparative Study.” Molecular Biology of the Cell (2008).
M.D. Dutt, M.R. Kasschau and S.K. Murphy. “Filopodia formation in the KG1a human hematopoietic cell lineand earthworm coelomocytes under hypertonic osmotic stress.”Molecular Biology of the Cell, submitted (2005).
C. E. O’Brien and S.K. Murphy. “Interaction between PKC and HSP 70 in Fibroblasts overexpressing cellular Ras.” Molecular Biology of the Cell, submitted (2005).
C. O’Brien*, D. Lakic* and S.K. Murphy. “HSP70 levels are elevated in fibroblasts overexpressing cellular Ras protein.” Molecular Biology of the Cell, 15:361a (2004).
M. Braun*, W. Ding* and S.K. Murphy. “Regulatory interactions of PIP2-PLC, PC-PLD and PKC in cultured mouse fibroblasts.” Molecular Biology of the Cell, 14:147a (2003).
S.K. Murphy, R. Kareem*, Y.Lai* and J. Worobiej*. “Effects of overexpression of cellular ras vs. mutated ras.” Molecular Biology of the Cell 11:242a (2000).
W.Ding*, Y. Kwok* and S.K. Murphy. “Reciprocal regulations of PI-PLC and PC-PLC/PLD in ras transformed fibroblasts.” Molecular Biology of the Cell 9:117a (1998).
S.A. Morine*, S.K. Murphy and M.R. Kasschau. Cytoskeletal changes in coelomocytes from the earthworm, Lumbricus Terrestris, stimulated to adhere to immobilized protein matrices. Molecular Biology of the Cell, 8:270a, (1997).
T.T. Ho*, T.M. Allen* and S.K. Murphy. Ras p21 regulates phospholipase D through the cAMP cascade. Molecular Biology of the Cell, 8:142a, (1997).
T. Ho* and S.K. Murphy. Regulation of phospholipase C and D by RAS p21 and Protein kinase C. Molecular Biology of the Cell, 7:343a (1996).
S.K. Murphy, S. Robb-Gaspers* and A.M. Haines*. Protein kinase C regulates the activity of phospholipase C and phospholipase D in ras-expressing and non-ras-expressing NIH3T3 cells. Proceedings of the American Association for Cancer Research, 36:53 (1995).
Memberships in Professional Organizations
American Society for Cell Biology
American Association for the Advancement of Science
National Association of Advisors for the Health Professions
(member Board of Directors 2000-2002, Secretary 2002-present)
Northeast Association of Advisors for the Health Professions
(member of Executive Board 1996-2000, President 2000-2001)
Association for Women in Science
Association for Women in Cancer Research
|Office location:||Griffith Hall Room 212C|
|Mailing address:||Box 112|
University of Sciences
600 South 43rd Street
Philadelphia, PA 19104-4495
s [dot] murphy [at] usciences [dot] edu