Dr. David Koh
Postdoctoral Fellow, Department of Neurology and Institute for Cell Engineering, Johns Hopkins
University School of Medicine, Baltimore, MD
Registered Pharmacist in Ohio, Pennsylvania, Kentucky
Other Experience and Professional Memberships
American Association for Cancer Research
American Society for Pharmacology and Experimental Therapeutics
American Association of Colleges of Pharmacy
American Chemical Society
Ph.D. in Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, KY
- Drug-induced mechanisms of cell death
- Central nervous system pharmacology
- GI and liver pharmacology
- Endocrine system pharmacology
- Molecular and cellular mechanisms of cell death
- Cell signaling events in response to toxic chemicals that determine cell fate
- Modulation of genomic integrity and cell death to improve breast cancer cell killing
Cells possess multiple mechanisms to respond to genomic stress, or damage to the genetic material required for normal functioning and development. These mechanisms usually end with either the return to normal cellular function after DNA repair or the induction of cell death. Between the detection of DNA damage and the life or death outcome, there are many signaling events. My laboratory is interested in the cellular and molecular mechanisms that ultimately determine these cell fates. Insight into these events should lead to better strategies to treat conditions caused by the inappropriate survival of cells, such as cancer.
My laboratory investigates these mechanisms by focusing on poly(ADP-ribosyl)ation, a unique but essential biochemical cycle in the cell. The two enzymes responsible for the progression of this nuclear cycle are poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG). Poly(ADP-ribosyl)ation is up-regulated immediately following DNA damage and has the important role of facilitating cell survival or initiating cell death. We are investigating the role of PARG in the modulation of caspase-mediated cell death, caspase-independent cell death, DNA repair, and chromatin dynamics.
A new focus of my lab is the investigation of calcium signaling in breast cancer cells. More specifically, we are investigating the ability of unique ion channels, known as transient receptor potential (TRP) channels, to allow breast cancer cells to survive and proliferate. A greater understanding of these channels in breast cancer cells will potentially allow the selective targeting of breast tumors with chemotherapy, and therefore facilitate improved tumor killing with minimal harmful effects in normal tissue.
Thus, my research seeks to identify and evaluate PARG, PARP-1, and TRP channels as therapeutic targets. Once characterized, targeting these proteins with pharmacologic agents is expected to have novel therapeutic value in treating breast cancer patients in the future.
Experimental techniques used in my laboratory include cell culture, PCR, molecular cloning, Western blotting, RNA interference, immunoprecipitation, flow cytometry and in vivo/in vitro chemotherapeutic models.
D.W. Koh, D.P. Powell, S.D. Blake, J.L. Hoffman, M.M. Hopkins, X. Feng (2015) Enhanced cytotoxicity in triple-negative and estrogen receptor-positive breast adenocarcinoma cells due to inhibition of the transient receptor potential melastatin-2 channel. International Journal of Oncology (currently in peer review)
M.M. Hopkins, X. Feng, M. Liu, L.P. Parker, D.W. Koh (2015). Inhibition of the transient receptor potential melastatin-2 channel causes increased DNA damage and decreased proliferation in breast adenocarcinoma cells. International Journal of Oncology 46: 2267-2276. PMID: 25760245
S.T. Dillon, M.K. Bhasin, X. Feng, D.W. Koh, S.S. Daoud (2013) Quantitative proteomic analysis in HCV-induced HCC reveals sets of proteins with potential significance for racial disparity. Journal of Translational Medicine 11(1): 239. PMID: 24283668
X. Feng and D.W. Koh (2013). Roles of poly(ADP-ribose) glycohydrolase in DNA damage and apoptosis. International Review of Cell and Molecular Biology 304: 227-81. PMID: 23809438
Feng, X. and D.W. Koh (2013). “Inhibition of poly(ADP-ribose) polymerase-1 or poly(ADP-ribose) glycohydrolase individually, but not in combination, leads to improved chemotherapeutic efficacy in Hela cells.” International Journal of Oncology 42(2): 749-756. PMID: 23254695
X. Feng, Y. Zhou, A.M. Proctor, M.M. Hopkins, M. Liu and D.W. Koh (2012). Silencing of apoptosis-inducing factor and poly(ADP-ribose) glycohydrolase reveals novel roles in breast cancer cell death after chemotherapy. Molecular Cancer 11(1): 48. PMID: 22839996
Y. Zhou and D.W. Koh (2011). Poly(ADP-ribosyl)ation Pathways in Mammals: The advantage of murine PARG null mutation. Methods in Molecular Biology 780: 337-348. PMID: 21870270
Y. Zhou, X. Feng and D.W. Koh (2011). Synergistic cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine and absence of poly(ADP-ribose) glycohydrolase involves chromatin decondensation. International Journal of Oncology 39(1): 121-127. PMID: 21519789
Y. Zhou, X. Feng and D.W. Koh (2011). Activation of cell death mediated by apoptosis-inducing factor due to the absence of poly(ADP-ribose) glycohydrolase. Biochemistry 50(14): 2850-2859. PMID: 21366272
Y. Zhou, X. Feng and D.W. Koh (2010). Enhanced DNA accessibility and increased DNA damage induced by the absence of poly(ADP-ribose) hydrolysis. Biochemistry 49(34): 7360-7366. PMID: 20687516
M.F. Poitras, D.W. Koh, S.W. Yu, S.A. Andrabi, A.S. Mandir, G.G. Poirier, V.L. Dawson and T.M. Dawson (2007). Spatial and functional relationship between poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in the brain. Neuroscience 148(1): 198-211. PMID: 17640816
S.A. Andrabi, N.S. Kim, S.W. Yu, H. Wang, D.W. Koh, M. Sasaki, J.A. Klaus, T. Otsuka, Z. Zhang, R.C. Koehler, P.D. Hurn, G.G. Poirier, V.L. Dawson and T.M. Dawson (2006). Poly(ADP-ribose) (PAR) polymer is a death signal. Proceedings of the National Academy of Sciences USA 103(48): 18308-18313. PMID: 17116882
D.W. Koh, A.M. Lawler, M.F. Poitras, M. Sasaki, S. Wattler, M.C. Nehls, T. Stoger, G.G. Poirier, V.L. Dawson and T.M. Dawson (2004). Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality. Proceedings of the National Academy of Sciences USA 101(51): 17699-17704. PMID: 15591342
D.W. Koh, D.L. Coyle, N. Mehta, S. Ramsinghani, H. Kim, J.T. Slama and M.K. Jacobson (2003). SAR analysis of adenosine diphosphate (hydroxymethyl)pyrrolidinediol inhibition of poly(ADP-ribose) glycohydrolase. Journal of Medicinal Chemistry 46(20): 4322-4332. PMID: 13678410
D.W. Koh, C.N. Patel, S. Ramsinghani, J.T. Slama, M.A. Oliveira and M.K. Jacobson (2003). Identification of an inhibitor binding site of poly(ADP-ribose) glycohydrolase. Biochemistry 42(17): 4855-4863. PMID: 12718526
Robertson-Evans Pharmacy Building 216
525 South Main Street
Ada, Ohio 45810
Tuesday: 8 a.m.-5 p.m.
Wednesday: 8 a.m.-5 p.m.
Thursday: 8 a.m.-5 p.m.
Friday: 8 a.m.-5 p.m.