DEPARTMENT:

Basic Sciences


CAMPUS AFFILIATION:

Doylestown


OFFICE:

Geisinger Commonwealth School of Medicine
Doylestown Campus
Pennsylvania Biotechnology Center of Bucks County
3805 Old Easton Road, Office 129
Doylestown, PA 18902


PHONE:

215-589-6357


FAX:

215-489-4920



EDUCATION:

BA (2001)  – Drew University, Madison, NJ
MS (2004) – New York University, New York, NY
PhD (2006) – New York University, New York, NY
Post doctorate (2009) – Naval Research Laboratory, Washington, DC


BIO:

John Kulp, PhD’s background is in the field of bioorganic chemistry with specialization in protein nuclear magnetic resonance (NMR) structure determination, computational methods for studying protein structure, synthetic peptide chemistry and computer-aided drug design with a focus on computational fragment-based methods. During his PhD, Dr. Kulp’s work centered on stabilizing alpha-helical peptides for development as a new class of drug molecules and using NMR to study peptide structure in solution and on solid surfaces. During his postdoctoral fellowship at the Naval Research Laboratory, he developed peptide nanopores as stochastic sensing elements and patented a new class of beta-helical peptide architectures.

Dr. Kulp left the Navy in 2010 to follow his research interests in therapeutic discovery. He joined BioLeap, a small business with a proprietary fragment-based computational chemistry software platform that specialized in the study of protein-protein interactions. Dr. Kulp participated in the development of novel inhibitors for DHFR, PCSK9, 11b-HSD and recA. 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).  During that time, he integrated molecular dynamics and docking software into BioLeap’s fragment-based discovery platform.

In 2014, Dr. Kulp founded Conifer Point Pharmaceuticals as a computational consulting company to help accelerate medicinal chemistry projects by increasing customer success in: hit identification, lead optimization, acquiring grant awards, attracting investment funding and attracting licensing or collaboration opportunities.

Dr. Kulp joined the Baruch S. Blumberg Institute, the Hepatitis B Foundation’s research arm, in 2013 as an assistant professor. He still maintains an active research lab that focuses on identifying and characterizing novel treatments for hepatitis B and liver cancer. In 2015, Dr. Kulp took on the additional role of director of academic affairs at the Blumberg Institute. Dr. Kulp oversees educational training at the institute, including high school programs, college internships, MS and PhD degrees, post-doctoral training and doctor of medicine education. Notably, Dr. Kulp coordinates the partnership between the Geisinger Commonwealth School of Medicine’s Master of Biomedical Science (MBS) program and the Baruch S. Blumberg Institute.


CLINICAL INTERESTS:

Hepatitis B and liver cancer

EDUCATIONAL INTERESTS:

Biochemistry, pharmacology, professional development, protein structure and function

RESEARCH INTERESTS:

Improving the potency and decreasing the toxicity of drugs through rigorous molecular design, Identifying new natural products and small molecules for the treatment of hepatitis B that specifically target unique points in the viral life cycle, including the formation of hepatitis B surface antigen (HBsAg) and covalently closed circular DNA (cccDNA), determining the basis for the selectivity of compounds targeting of liver cancer cells versus non-liver cancer cell lines

STUDENT RESEARCH OPPORTUNITIES:

Screening a collection of small molecules for hepatitis B surface antigen and cccDNA inhibitors using alphaLISA and ELISA assay, validating and studying the mechanism of action of potent, nontoxic compounds that appear to target hepatitis B virus


PUBLICATIONS:

  1. Cloudsdale IS, Dickson JK Jr, Barta TE, Grella BS, Smith ED, Kulp JL 3rd, Guarnieri F, Kulp JL Jr. Design, synthesis and biological evaluation of renin inhibitors guided by simulated annealing of chemical potential simulations. Bioorg Med Chem. 2017 Aug 1;25(15):3947-3963. doi: 10.1016/j.bmc.2017.05.032. Epub 2017 May 19. PubMed PMID: 28601508.

  2. Wu S, Zhao Q, Zhang P, Kulp J, Hu L, Hwang N, Zhang J, Block TM, Xu X, Du Y, Chang J, Guo JT. Discovery and mechanistic study of benzamide derivatives that modulate hepatitis B virus capsid assembly. J Virol. 2017 May 31. pii: JVI.00519-17. doi: 10.1128/JVI.00519-17. [Epub ahead of print] PubMed PMID: 28566379.

  3. Guo F, Wu S, Julander J, Ma J, Zhang X, Kulp J, Cuconati A, Block TM, Du Y, Guo JT, Chang J. A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein. J Virol. 2016 Sep 21. pii: JVI.01253-16. PMID: 27654301, PMCID: PMC5110185
  1. Emert-Sedlak LA, Loughran HM, Shi H, Kulp JL 3rd, Shu ST, Zhao J, Day BW, Wrobel JE, Reitz AB, Smithgall TE. Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists. Bioorg Med Chem Lett. 2016 Mar 1;26(5):1480-4. doi: 10.1016/j.bmcl.2016.01.043. PMID: 26852364, PMCID: PMC4756635
  1. Morgnanesi D, Heinrichs EJ, Mele AR, Wilkinson S, Zhou S, Kulp JL 3rd. A computational chemistry perspective on the current status and future direction of hepatitis B antiviral drug discovery. Antiviral Res. 2015 Nov;123:204-15. doi: 10.1016/j.antiviral.2015.10.014. Review. PMID: 26477294
  1. Seker UO, Wilson B, Kulp JL, Evans JS, Tamerler C, Sarikaya M. Thermodynamics of engineered gold binding peptides: establishing the structure-activity relationships. Biomacromolecules. 2014 Jul 14;15(7):2369-77. doi: 10.1021/bm4019006. PMID: 24892212
  1. Kulp JL 3rd, Blumenthal SN, Wang Q, Bryan RL, Guarnieri F. A fragment-based approach to the SAMPL3 Challenge. J Comput Aided Mol Des. 2012 May;26(5):583-94. doi: 10.1007/s10822-012-9546-1. PMID: 22290624
  1. Fears KP, Photiadis SJ, Kulp JL 3rd, Clark TD. Synthesis and characterization of cyclic peptides that are β-helical in trifluoroethanol. J Pept Sci. 2014 May;20(5):366-74. doi: 10.1002/psc.2623. PMID: 24648029
  1. Kulp JL 3rd, Kulp JL Jr, Pompliano DL, Guarnieri F. Diverse fragment clustering and water exclusion identify protein hot spots. J Am Chem Soc. 2011 Jul 20;133(28):10740-3. doi: 10.1021/ja203929x. PMID: 21682273
  1. Kulp JL 3rd, Owrutsky JC, Petrovykh DY, Fears KP, Lombardi R, Nafie LA, Clark TD. Vibrational circular-dichroism spectroscopy of homologous cyclic peptides designed to fold into β helices of opposite chirality. Biointerphases. 2011 Mar;6(1):1-7. doi: 10.1116/1.3548075. PMID: 21428689
  1. Bernstein N, Kulp JL 3rd, Cato MA Jr, Clark TD. Simulations of nanocylinders self-assembled from cyclic β-tripeptides. J Phys Chem A. 2010 Nov 11;114(44):11948-52. doi: 10.1021/jp103447w. PMID: 20961136
  1. Barlow DE, Dickinson GH, Orihuela B, Kulp JL 3rd, Rittschof D, Wahl KJ. Characterization of the adhesive plaque of the barnacle Balanus amphitrite: amyloid-like nanofibrils are a major component. Langmuir. 2010 May 4;26(9):6549-56. doi: 10.1021/la9041309. PMID: 20170114
  1. Kulp III John L, Clark TD. Innovative Foldamers: Engineering Heterochiral Peptides NRL Review. 2010; 2009:149-150.
  1. Kulp JL 3rd, Clark TD. Engineering a beta-helical D,L-peptide for folding in polar media. Chemistry. 2009 Nov 9;15(44):11867-77. doi: 10.1002/chem.200901129. PMID: 19784965
  1. So CR, Kulp JL, Oren EE, Zareie H, Tamerler C, Evans JS, Sarikaya M. Molecular recognition and supramolecular self-assembly of a genetically engineered gold binding peptide on Au{111}. ACS Nano. 2009 Jun 23;3(6):1525-31. doi: 10.1021/nn900171s. PMID: 19438257
  1. Chapman R, Kulp JL 3rd, Patgiri A, Kallenbach NR, Bracken C, Arora PS. Trapping a folding intermediate of the alpha-helix: stabilization of the pi-helix. Biochemistry. 2008 Apr 8;47(14):4189-95. doi: 10.1021/bi800136m. PMID: 18335996
  1. O’Shaughnessy TJ, Hu JE, Kulp JL 3rd, Daly SM, Ligler FS. Laser ablation of micropores for formation of artificial planar lipid bilayers. Biomed Microdevices. 2007 Dec;9(6):863-8. PMID: 17574531
  1. Kulp JL 3rd, Minamisawa T, Shiba K, Tejani M, Evans JS. Structural properties of an artificial protein that regulates the nucleation of inorganic and organic crystals. Langmuir. 2007 Mar 27;23(7):3857-63. PMID: 17309282
  1. Wang D, Chen K, Kulp Iii JL, Arora PS. Evaluation of biologically relevant short alpha-helices stabilized by a main-chain hydrogen-bond surrogate. J Am Chem Soc. 2006 Jul 19;128(28):9248-56. PMID: 16834399, PMCID: PMC1828873
  1. Kulp JL 3rd, Shiba K, Evans JS. Probing the conformational features of a phage display polypeptide sequence directed against single-walled carbon nanohorn surfaces. Langmuir. 2005 Dec 6;21(25):11907-14. PMID: 16316132
  1. Kase D, Kulp JL 3rd, Yudasaka M, Evans JS, Iijima S, Shiba K. Affinity selection of peptide phage libraries against single-wall carbon nanohorns identifies a peptide aptamer with conformational variability. Langmuir. 2004 Sep 28;20(20):8939-41. No abstract available. PMID: 15379530
  1. Kulp John L, Sarikaya M, Evans JS. Molecular Characterization of a Prokaryotic Polypeptide Sequence that Catalyzes Au Crystal Formation. Journal of Material Chemistry. 2004 April 22; 14(14):2325.