John Kulp, PhD
Blumberg Institute Associate Professor (Principal Investigator)
Director of Academic Affairs
Ph: (215) 589- 6357
(2006) Ph.D., New York University, New York, NY
(2009) Post doctorate, Naval Research Laboratory, Washington, DC
Appointment at the Baruch S. Blumberg Institute: Dr. Kulp is an Associate Professor in the Department of Medicinal Chemistry and the Director of Academic Affairs.
Other appointments: CEO, Conifer Point Pharmaceuticals; CSO Small Molecule PPI Mimetics
Research interest: Dr. Kulp’s vision is to create better drugs by rigorous molecular design.
Research staff: Professors Tianlun Zhou, Tim Block, and other faculty at the Blumberg Institute
Fellows and Students: John Rogowskyj, Ella Mullikin, Kishan Bhut, Rachel Swope
The Kulp laboratory accesses two extraordinary resources at the center: The Blumberg’s Natural Products Discovery Institute (NPDI), which houses a vast natural products collection (former Merck and Schering Plough Collection), and the Baruch S. Blumberg Institute’s faculty that developed world class assays for the hepatitis B virus (HBV) and hepatocellular carcinoma (liver cancer). The U.S. Natural Product Library has a track record of yielding novel bioactive compounds. Some have led to “blockbuster” drugs such as Primaxin®, Mevacor®, Ivomec®, and Cancidas®. Indeed, natural products are the source of 50% of marketed drugs. One goal of the lab is to identify new natural products for the treatment of hepatitis B that specifically target unique points in the viral life cycle including cccDNA silencing. To achieve a functional cure for hepatitis B, or at least a sustained virological response without treatment, will require either (i) suppression of the integrated DNA (cccDNA) or (ii) a multi-target approach with the outcome of a prolonged virological suppression. The end products of the research will be novel natural products that are effective against the HBV and could be used in combination.
Another project in the Kulp lab is aimed at determining the basis for the selectivity of compounds targeting of liver cancer cells versus non-liver cancer cell lines, in tissue culture. The compounds are selectively toxic to HepG2, Huh7 and other liver cancer lines, relative to “non-cancerous” liver lines THLE2, PH5CH and even more than 20 other cancer lines that are of other organs.
Dr. Kulp’s background is in the field of bioorganic chemistry with specialization in (i) protein nuclear magnetic resonance (NMR) structure determination, (ii) computational methods for studying protein structure, (iii) synthetic peptide chemistry, and (iv), computer-aided drug design with a specialty focus on computational fragment-based methods. His Ph.D. work, in part, concentrated on stabilizing a-helical peptides for development as a new class of drug molecules and the study of peptide/protein structure in solution and on solid surfaces by NMR. During his postdoctoral training at the Naval Research Laboratory, he developed peptide nanopores as stochastic sensing elements and patented a new class of b-helical peptide architectures. After completing his postdoctoral fellowship, Dr. Kulp was hired as a federal staff scientist where he helped develop a program to study biointerfaces. He chose to leave the Navy and follow his research interests in therapeutic discovery. In 2010, Dr. Kulp joined BioLeap, a small business that specializes in protein-protein interactions and that had a proprietary fragment-based computational chemistry software platform. He participated in development of novel inhibitors for DHFR, PCSK9, 11b-HSD, and recA. During that time, he integrated molecular dynamics and docking software into BioLeap’s proprietary fragment-based discovery platform. From 2013 to 2014, Dr. Kulp was the project leader for BioLeap’s PCSK9 program, which consisted of modeling (BioLeap), assays (Broad Institute of MIT and Harvard), and chemical synthesis (WuXi and BioDuro). In 2014, Dr. Kulp founded Conifer Point Pharmaceuticals as a computational consulting company to help accelerate medicinal chemistry projects and increase customer success in: hit identification, lead qualification/optimization, and likelihood of grant awards, attracting investment funding, or licensing/collaboration opportunities. Dr. Kulp joined the Blumberg Institute in 2013 as an Assistant Professor.
In addition to his active investigation program, Dr. Kulp, as Director of Academics, oversees educational training at the institute. This includes high school programs, college internships, MS and PhD degrees, post-doctoral training, and doctor of medicine education.
Design and development of therapeutic strategies, to be used in combination, for treatment of hepatitis B virus (HBV).
“A computational chemistry perspective on the current status and future direction of hepatitis B antiviral drug discovery.,” D. Morgnanesi, E.J. Heinrichs, A.R. Mele, S. Wilkinson, S. Zhou, J.L. Kulp III, Antiviral Research 2015 123, 204-215.
“Synthesis and characterization of cyclic peptides that are β-helical in trifluoroethanol.” K.P. Fears, S.J. Photiadis, J.L. Kulp III and T.D. Clark, Journal of Peptide Science 2014 20(5), 366-374.
“A Fragment-based Approach to the SAMPL3 Challenge.” J.L. Kulp III, S.N. Blumenthal, Q. Wang, R. Bryan, F. Guarnieri, Journal of Computer-Aided Molecular Design 2012 26(5), 583-594.
“Diverse Fragment Clustering and Water Exclusion Identify Protein Hot Spots,” J.L. Kulp III, J.L. Kulp Jr., D.L. Pompliano, F. Guarnieri, Journal of the American Chemical Society 2011 133(28), 10740-1074.
Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/john.kulp.2/