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  • Fast-Track: Sickle Cell Drug Targets Key Enzyme

    Woster research an awardee in Sickle Cell Disease/Advancing Cures funding; fast-track research focused on developing a new gene-modifying sickle cell disease treatment at MUSC could lead to human clinical trials in as few as three years.

  • Nappi and Haney Honored at MUSC Convocation

    Jean Nappi (MUSC Foundation Distinguished Faculty Service Award) and Jason Haney (MUSC Teaching Excellence Award in Educator-Mentor:Clinical/Professional) were recognized for excellence during the 2017 MUSC Faculty Convocation.
     
  • drug discovery

    The College

    The College of Pharmacy at the Medical University of South Carolina provides a premier pharmacy education leveraging the innovative inter-professional learning opportunities offered at South Carolina’s only comprehensive academic health center with a full range of programs in the biomedical sciences.


  • Welcome Home Weekend

    Registration for MUSC College of Pharmacy Welcome Home Weekend is now live! Festivities include the Vincent T. Peng Endowed Lectureship (CE), lunch with the dean, a day-in-the-life panel with current students and the traditional Lowcountry Oyster Roast. Visit the Welcome Home website for information.

     

  • Mikell Named MUSC Pharmacy Honorary Alumnus of the Year

    The 2017 White Coat Ceremony featured as keynote speaker Nancy G. Mikell, who was also presented with the Honorary Alumnus of the Year Award. Mikell's address was the highlight of a week of 2017 Orientation activities capped by the ceremony at Baruch Auditorium August 17.   

  • Clinical Pharmacy and Outcomes Science

    Faculty nationally recognized for achievement in both teaching and practice provide interprofessional education and training in patient care, critical thinking and professional leadership.


Drug Discovery & Biomedical Sciences

The Department of Drug Discovery and Biomedical Sciences (DDBS) provides training in the basic sciences to professional (PharmD) and graduate students (Ph.D.). Training provides fundamentals in the health sciences including; biochemistry, cell and molecular biology, pharmacology, oncology and neuroscience. Research training in DDBS encompasses the understanding of disease mechanisms, drug action and toxicity, the design and development of new pharmaceutical agents, and the identification of new drug targets. Graduates of the program (Pharm.D/Ph.D. or Ph.D.) can pursue diverse and exciting career opportunities in academia, pharmaceutical and biotechnology companies, or with government agencies. DDBS has 14 faculty members. 

Research efforts in DDBS include the following areas: chemical biology/medicinal chemistry, translational cancer therapeutics, mitochondrial biology, cell death, injury and regeneration, pharmacogenomics, targeted therapeutics, pharmacology, neuroscience, and personalized medicine.

Highlights

Eduardo Maldonado has been awarded a five-year, $1.1 million RO1 grant from the National Institutes of Health (NIH). The American Association for the Study of Liver Diseases selected his research for Presidential Distinction during the 2015 Annual Liver Meeting in San Francisco. The research focuses on the bioenergetics of cells and may create a new paradigm for cancer treatment by targeting mitochondria to revert the Warburg metabolism, which is a common feature for most types of cancer.

 

 

Mark Hamann has been named the Carol and Charles Cooper Endowed Chair in Pharmacy at MUSC. The drug discovery pipeline the new SmartState™ chair brings to the Center of Economic Excellence in Drug Discovery includes an extract from Hawaiian algae that could be effective against breast cancers resistant to chemotherapy; a never-described molecule from a standard lemon’s zest that might be able to replace a common synthetic yellow color dye; and some 30 new compounds from a deep sea sponge the team collected off the Aleutian Isles, requiring submersibles to explore the oceans bottom.


 

GlaxoSmithKline Distinguished Endowed Chair of Pharmacy John Lemasters, an internationally renowned expert on microscopy, was awarded $1.5 million this past year in NIH R01 grants, including a shared instrument grant for an upgrade to a Zeiss 880 NLO confocal/ multiphoton microscope. The application is to upgrade of a 9-year old Zeiss LSM 510 NLO microscope to a state-of-the art Zeiss LSM 880 NLO confocal/multiphoton microscope.

Research

Sherine Chan has been named coordinator of the graduate program. Recently promoted to associate professor of drug discovery and biomedical sciences, she is responsible for recruitment, retention and matriculation of DDBS graduate students. She also serves as liaison to the MUSC Graduate Council.

Graduate Program

The Doctor of Philosophy degree is considered the mark of highest achievement in preparation for creative scholarship and research. It is the highest degree conferred by our universities and, by nature and tradition, is a research degree.

Doctor of Philosophy Program Objectives and Requirements

Research Centers and Initiatives

The Center for Cell Death, Injury and Regeneration

The Center for Cell Death, Injury and Regeneration which was established in 2007 is headed by John J. Lemasters. The center provides imaging facility through the use of six confocal/multiphoton microscopes which are also a part of the Hollings Cell and Molecular Imaging Facility. The center also is home to a multiwell plate reader and Seahorse Bioscience facility. Anna-Liisa Nieminen is co-director of the imaging facility. Raymond Deepe, assists with the day to day running of the facility. 

In addition the center also houses imaging workstations, surgery benches and tissue culture hoods for specimen preparation and data analysis.

Center for Cancer Drug Discovery 

The Cancer Drug Discovery Center provides mechanisms for target identification and generation of lead compounds in the drug discovery process, thus creating a productive interface between academics and the biotechnology/pharmaceutical industries.
 

Medication Safety

The Doris Lesvkoff Meddin Medication Safety Education Program is an education and outreach program designed to help reduce adverse drug effects by disseminating current and emerging knowledge about ADEs to healthcare professionals and the general public.

SCORxE

The South Carolina Medicaid Academic Detailing Program is officially identified as SCORxE which stands for South Carolina Offering Prescribing Excellence. Our mission is to improve the quality of care for South Carolina Medicaid patients in the most cost effective manner by promoting quality, evidence-based drug therapy and best practices through face-to-face communication with providers.

Endowed Chairs

Dr. John J. Lemasters

GlaxoSmithKline Distinguished Endowed Chair at MUSC, CoEE in Cancer Drug Discovery

Lemasters is a pioneer of techniques that allow scientists to see what happens inside an individual cell during reoxygenation—the restoration of oxygen to an organ following oxygen deprivation, which sometimes occurs following a heart attack or stroke. The process of redistributing oxygen to an organ can be stressful on tissue, leading to possible trauma and even cell death. Lemasters specializes in a kind of microscopy that allows scientists to view slices of an individual cell, much like CAT or MRI scans complement the more traditional X-ray by allowing doctors to view the body in layers. Other applications for Lemasters’ work include understanding the mechanisms through which the liver is injured by chronic alcohol use and donated organs are damaged while being held for transplant surgery. Lemasters is director of the Center for Cell Death, Injury and Regeneration. The Center for Cell Death, Injury and Regeneration was established in 2006 and provides imaging facility through the use of five confocal microscopes which are also a part of the Hollings Cell and Molecular Imaging Facility. The center also is home to a multiwell plate reader. Ongoing projects in the center’s laboratory using the microscopes include Intravital Imaging of Liver Function using Multiphoton Microscopy, Autophagy/Mitophagy, Mitochondrial Permeability Transition (MPT) and Luminescence Lifetime Imaging Microscopy.

Dr. Patrick Woster

Endowed Chair in Medicinal Chemistry

Woster is one of the nation's leading cancer drug researchers and is working to develop drugs that turn specific genes on or off in tumor cells, a process known as epigenetic modulation that can make anti-tumor medications more effective. In addition, he and his team are working to discover new treatments for diseases such as malaria and other parasitic illnesses. Woster holds eight patents based on compounds he has synthesized. His work could have a notable impact on quality of life in South Carolina by leading to improvements in both the physical well-being of cancer patients and in the economic health of the state through the creation of new companies and new job opportunities. As an example, he and his team recently made some discoveries in epigenetics – changes in gene expression that are not mediated through changing the actual sequence of DNA – including an enzyme that helps control the process of gene expression. They then discovered some compounds that inhibit the enzyme and cause tumor cells to re-express tumor-suppressant proteins, thus essentially converting a tumor cell back into a normal, more easily treated cell.

Dr. Mark Hamann

Charles and Carol Cooper Endowed Chair

Mark Hamann is the Charles and Carol Cooper Chair in Pharmacy Endowed SmartState Chair in the Cancer Drug Discovery Center of Economic Excellence. His team looks at the role of natural products in the discovery and development of therapeutics. It focuses on the discovery and development of new treatments for drug resistant cancer and infectious diseases from natural product prototypes. His group has identified potential new and innovative solutions to pancreatic cancer, leukemia, breast and lung cancer as well as MRSA and depression.

DDBS Recent Publications

1. Alhasson, F., Dattaroy, D., Das, S., Chandrashekaran, V., Seth, R. K., Schnellmann, R. G., and Chatterjee, S. (2016) NKT cell modulates NAFLD potentiation of metabolic oxidative stress-induced mesangial cell activation and proximal tubular toxicity. Am. J. Physiol. Renal Physiology 310, F85-F101
2. Azarashvili, T., Krestinina, O., Baburina, Y., Odinokova, I., Grachev, D., Papadopoulos, V., Akatov, V., Lemasters, J. J., and Reiser, G. (2015) Combined effect of G3139 and TSPO ligands on Ca(2+)-induced permeability transition in rat brain mitochondria. Arch. Biochem. Biophys. 587, 70-77
3. Baarine, M., Beeson, C., Singh, A., and Singh, I. (2015) ABCD1 deletion-induced mitochondrial dysfunction is corrected by SAHA: implication for adrenoleukodystrophy. J. Neurochem. 133, 380-396
4. Belosludtsev, K. N., Belosludtseva, N. V., Agafonov, A. V., Penkov, N. V., Samartsev, V. N., Lemasters, J. J., and Mironova, G.D. (2015) Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions. Biochim. Biophys. Acta 1848, 2200-2205
5. Bestman, J. E., Stackley, K. D., Rahn, J. J., Williamson, T. J., and Chan, S. S. (2015) The cellular and molecular progression of mitochondrial dysfunction induced by 2,4-dinitrophenol in developing zebrafish embryos. Differentiation; Research in Biological Diversity 89, 51-69
6. Bohovych, I., Fernandez, M. R., Rahn, J. J., Stackley, K. D., Bestman, J. E., Anandhan, A., Franco, R., Claypool, S. M., Lewis, R.E., Chan, S. S., and Khalimonchuk, O. (2015) Metalloprotease OMA1 Fine-tunes Mitochondrial Bioenergetic Function and Respiratory Supercomplex Stability. Sci. Rep. 5, 13989
7. Chaturvedi, R., de Sablet, T., Asim, M., Piazuelo, M. B., Barry, D. P., Verriere, T. G., Sierra, J. C., Hardbower, D. M., Delgado, A.G., Schneider, B. G., Israel, D. A., Romero-Gallo, J., Nagy, T. A., Morgan, D. R., Murray-Stewart, T., Bravo, L. E., Peek, R. M., Jr., Fox, J. G., Woster, P. M., Casero, R. A., Jr., Correa, P., and Wilson, K. T. (2015) Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase. Oncogene 34, 3429-3440
8. Chatwichien, J., Basu, S., Murphy, M. E., Hamann, M. T., and Winkler, J. D. (2015) Design, Synthesis and Biological Evaluationof beta-Carboline Dimers Based on the Structure of Neokauluamine. Tet. Lett. 56, 3515-3517
9. Conway, S. J., Woster, P. M., Shen, J.-K., Georg, G., and Wang, S. (2015) Epigenetics: Novel therapeutics targeting epigenetics. J. Med. Chem. 58, 523-524
10. Cunningham, K. F., Beeson, G. C., Beeson, C. C., Baicu, C. F., Zile, M. R., and McDermott, P. J. (2015) Estrogen-Related Receptor alpha (ERRalpha) is required for adaptive increases in PGC-1 isoform expression during electrically stimulated contraction of adult cardiomyocytes in sustained hypoxic conditions. Int'l. J. Cardiology 187, 393-400
11. Dupre, T. V., Doll, M. A., Shah, P. P., Sharp, C. N., Kiefer, A., Scherzer, M. T., Saurabh, K., Saforo, D., Siow, D., Casson, L., Arteel, G. E., Jenson, A. B., Megyesi, J., Schnellmann, R. G., Beverly, L. J., and Siskind, L. J. (2016) Suramin protects from cisplatin-induced acute kidney injury. Am. J. Physiol. - Renal Phys. 310, F248-258
12. Galluzzi, L., Bravo-San Pedro, J. M., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Alnemri, E. S., Altucci, L., Andrews, D., Annicchiarico-Petruzzelli, M., Baehrecke, E. H., Bazan, N. G., Bertrand, M. J., Bianchi, K., Blagosklonny, M. V., Blomgren, K., Borner, C., Bredesen, D. E., Brenner, C., Campanella, M., Candi, E., Cecconi, F., Chan, F. K., Chandel, N. S., Cheng, E. H., Chipuk, J. E., Cidlowski, J. A., Ciechanover, A., Dawson, T. M., Dawson, V. L., De Laurenzi, V., De Maria, R., Debatin, K. M., Di Daniele, N., Dixit, V. M., Dynlacht, B. D., El-Deiry, W. S., Fimia, G. M., Flavell, R. A., Fulda, S., Garrido, C., Gougeon, M. L., Green, D. R., Gronemeyer, H., Hajnoczky, G., Hardwick, J. M., Hengartner, M. O., Ichijo, H., Joseph, B., Jost, P. J., Kaufmann, T., Kepp, O., Klionsky, D. J., Knight, R. A., Kumar, S., Lemasters, J. J., Levine, B., Linkermann, A., Lipton, S. A., Lockshin, R. A., Lopez-Otin, C., Lugli, E., Madeo, F., Malorni, W., Marine, J. C., Martin, S. J., Martinou, J. C., Medema, J. P., Meier, P., Melino, S., Mizushima, N., Moll, U., Munoz-Pinedo, C., Nunez, G., Oberst, A., Panaretakis, T., Penninger, J. M., Peter, M. E., Piacentini, M., Pinton, P., Prehn, J. H., Puthalakath, H., Rabinovich, G. A., Ravichandran, K. S., Rizzuto, R., Rodrigues, C. M., Rubinsztein, D. C., Rudel, T., Shi, Y., Simon, H. U., Stockwell, B. R., Szabadkai, G., Tait, S. W., Tang, H. L., Tavernarakis, N., Tsujimoto, Y., Vanden Berghe, T., Vandenabeele, P., Villunger, A., Wagner, E. F., Walczak, H., White, E., Wood, W. G., Yuan, J., Zakeri, Z., Zhivotovsky, B., Melino, G., and Kroemer, G. (2015) Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Diff. 22, 58-73
13. Gogineni, V., Schinazi, R. F., and Hamann, M. T. (2015) Role of Marine Natural Products in the Genesis of Antiviral Agents. Chem. Rev. 115, 9655-9706
14. Gong, J., Fields, M. A., Moreira, E. F., Bowrey, H. E., Gooz, M., Ablonczy, Z., and Del Priore, L. V. (2015) Differentiation of Human Protein-Induced Pluripotent Stem Cells toward a Retinal Pigment Epithelial Cell Fate. PloS One 10, e0143272
15. Gu, X., Wei, Z. Z., Espinera, A., Lee, J. H., Ji, X., Wei, L., Dix, T. A., and Yu, S. P. (2015) Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats. Exp. Neurol. 267, 135-142
16. Hammond, C. E., Beeson, C., Suarez, G., Peek, R. M., Jr., Backert, S., and Smolka, A. J. (2015) Helicobacter pylori virulence factors affecting gastric proton pump expression and acid secretion. Am. J. Physiol. Gastrointestinal and Liver physiology 309, G193-201
17. Hoye, T. R., Alarif, W. M., Basaif, S. S., Abo-Elkarm, M., Hamann, M. T., Wahba, A. E., and Ayyad, S. N. (2015) New cytotoxic cyclic peroxide acids from sp. marine sponge. ARKIVOC : Free Online J. Org. Chem. 2015, 164-175
18. Jayasundara, N., Kozal, J. S., Arnold, M. C., Chan, S. S., and Di Giulio, R. T. (2015) High-Throughput Tissue Bioenergetics Analysis Reveals Identical Metabolic Allometric Scaling for Teleost Hearts and Whole Organisms. PloS One 10, e0137710
19. Leonard, A. P., Cameron, R. B., Speiser, J. L., Wolf, B. J., Peterson, Y. K., Schnellmann, R. G., Beeson, C. C., and Rohrer, B.(2015) Quantitative analysis of mitochondrial morphology and membrane potential in living cells using high-content imaging, machine learning, and morphological binning. Biochim. Biophys. Acta 1853, 348-360
20. Li, Y., and Woster, P. M. (2015) Discovery of a new class of histone deacetylase inhibitors with a novel zinc binding group. MedChemComm 6, 613-618
21. Liu, Q., Krishnasamy, Y., Rehman, H., Lemasters, J. J., Schnellmann, R. G., and Zhong, Z. (2015) Disrupted Renal Mitochondrial Homeostasis after Liver Transplantation in Rats. PloS One 10, e0140906
22. Liu, Q., Rehman, H., Krishnasamy, Y., Schnellmann, R. G., Lemasters, J. J., and Zhong, Z. (2015) Improvement of liver injury and survival by JNK2 and iNOS deficiency in liver transplants from cardiac death mice. J. Hepatology 63, 68-74
23. Maganti, A. V., Maier, B., Tersey, S. A., Sampley, M. L., Mosley, A. L., Ozcan, S., Pachaiyappan, B., Woster, P. M., Hunter, C.S., Stein, R., and Mirmira, R. G. (2015) Transcriptional activity of the islet beta cell factor Pdx1 is augmented by lysine methylation catalyzed by the methyltransferase Set7/9. J. Biol. Chem. 290, 9812-9822
24. Mani, S. K., Kern, C. B., Kimbrough, D., Addy, B., Kasiganesan, H., Rivers, W. T., Patel, R. K., Chou, J. C., Spinale, F. G., Mukherjee, R., and Menick, D. R. (2015) Inhibition of class I histone deacetylase activity represses matrix metalloproteinase-2 and -9 expression and preserves LV function postmyocardial infarction. Am. J. Physiol. 308, H1391-1401
25. Nowotarski, S. L., Pachaiyappan, B., Holshouser, S. L., Kutz, C. J., Li, Y., Huang, Y., Sharma, S. K., Casero, R. A., Jr., and Woster, P. M. (2015) Structure-activity study for (bis)ureidopropyl- and (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon backbone architectures. Bioorg. Med. Chem. 23, 1601-1612
26. Patrick, K. S., Straughn, A. B., Reeves, O. T., 3rd, Bernstein, H., and Malcolm, R. (2015) Comparative Ethanol-Induced Potentiation of Stimulatory Responses to Dexmethylphenidate Versus Methylphenidate. J. Clin. Psychopharmacol. 35, 464-467
27. Rahn, J. J., Bestman, J. E., Stackley, K. D., and Chan, S. S. (2015) Zebrafish lacking functional DNA polymerase gamma survive to juvenile stage, despite rapid and sustained mitochondrial DNA depletion, altered energetics and growth. Nucleic Acids Res. 43, 10338-10352
28. Renaud, L., Harris, L. G., Mani, S. K., Kasiganesan, H., Chou, J. C., Baicu, C. F., Van Laer, A., Akerman, A. W., Stroud, R. E., Jones, J. A., Zile, M. R., and Menick, D. R. (2015) HDACs Regulate miR-133a Expression in Pressure Overload-Induced Cardiac Fibrosis. Circulation. Heart Failure 8, 1094-1104
29. Seremwe, M., Schnellmann, R. G., and Bollag, W. B. (2015) Calpain-10 Activity Underlies Angiotensin II-Induced Aldosterone Production in an Adrenal Glomerulosa Cell Model. Endocrinology 156, 2138-2149
30. Smith, J. A., Stallons, L. J., Collier, J. B., Chavin, K. D., and Schnellmann, R. G. (2015) Suppression of mitochondrial biogenesis through toll-like receptor 4-dependent mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling in endotoxin-induced acute kidney injury. J. Pharmacol. Exp. Ther. 352, 346-357
31. Subathra, M., Korrapati, M., Howell, L. A., Arthur, J. M., Shayman, J. A., Schnellmann, R. G., and Siskind, L. J. (2015) Kidney glycosphingolipids are elevated early in diabetic nephropathy and mediate hypertrophy of mesangial cells. Am. J. Physiol.- Renal Phys. 309, F204-215
32. Verlinden, B. K., de Beer, M., Pachaiyappan, B., Besaans, E., Andayi, W. A., Reader, J., Niemand, J., van Biljon, R., Guy, K., Egan, T., Woster, P. M., and Birkholtz, L. M. (2015) Interrogating alkyl and arylalkylpolyamino (bis)urea and (bis)thiourea isosteres as potent antimalarial chemotypes against multiple lifecycle forms of Plasmodium falciparum parasites. Bioorg.
Med. Chem. 23, 5131-5143
33. Wang, B., Waters, A. L., Valeriote, F. A., and Hamann, M. T. (2015) An efficient and cost-effective approach to kahalalide FN-terminal modifications using a nuisance algal bloom of Bryopsis pennata. Biochim. Biophys. Acta 1850, 1849-1854
34. Waters, A. L., Oh, J., Place, A. R., and Hamann, M. T. (2015) Stereochemical Studies of the Karlotoxin Class Using NMR Spectroscopy and DP4 Chemical-Shift Analysis: Insights into their Mechanism of Action. Angewandte Chemie 54, 15705-15710
35. Whitaker, R. M., Corum, D., Beeson, C. C., and Schnellmann, R. G. (2016) Mitochondrial Biogenesis as a Pharmacological Target: A New Approach to Acute and Chronic Diseases. Ann. Rev. Pharmacol. Toxicol. 56, 229-249
36. Whitaker, R. M., Korrapati, M. C., Stallons, L. J., Jesinkey, S. R., Arthur, J. M., Beeson, C. C., Zhong, Z., and Schnellmann, R. G.(2015) Urinary ATP Synthase Subunit beta Is a Novel Biomarker of Renal Mitochondrial Dysfunction in Acute Kidney Injury.Toxicol. Sci. 145, 108-117
37. Whitaker, R. M., Stallons, L. J., Kneff, J. E., Alge, J. L., Harmon, J. L., Rahn, J. J., Arthur, J. M., Beeson, C. C., Chan, S. L., and Schnellmann, R. G. (2015) Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal dysfunction in acute kidney injury. Kidney international 88, 1336-1344
38. Wills, L. P., Beeson, G. C., Hoover, D. B., Schnellmann, R. G., and Beeson, C. C. (2015) Assessment of ToxCast Phase II for Mitochondrial Liabilities Using a High-Throughput Respirometric Assay. Toxicol. Sci. 146, 226-234
39. Woster, P. M. (2015) A history of Annual Reports in Medicinal Chemistry Ann. Rep. Med. Chem. 50, 1-14
40. Yuan, H., Wang, X., Hill, K., Chen, J., Lemasters, J. J., Yang, S. M., and Sha, S. H. (2015) Autophagy attenuates noise-induced hearing loss by reducing oxidative stress. Antiox. Redox Signaling 22, 1308-1324

 
Fighting sickle cell disease by looking to babyhood
Oct 12, 2017 6:32:00 PM EDT

Fast-track research focused on developing a new gene-modifying sickle cell disease treatment at the Medical University of South Carolina could lead to human clinical trials in as few as three years....Read more...

 
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