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John Karanicolas, PhD

John Karanicolas, PhD
About

Associate Professor

Director, Postdoctoral and Graduate Student Training Program

Research Program

Designing Protein Switches and Sensors
Important advances in cell biology have been enabled though selective activation of proteins involved in glycosylation, nuclear import/export, proteolysis, signaling across the cell membrane, and cell suicide.
Modulating Protein Function with Small Molecules, Using Computational and Experimental Design Techniques
Our primary goal is to develop structure-based approaches for modulating protein function using small-molecules. We are exploring two parallel paths towards this overarching goal: the first is re-engineering proteins so that a small-molecule can be used to “turn on” function, and the second is identifying small-molecules that naturally complement and occlude a protein surface to “turn off” function. We apply these tools to understand how specific protein interactions are responsible for normal and aberrant signal transduction in cells.

 

Education and Training

Educational Background

  • PhD, Macromolecular and Cellular Structure and Chemistry, The Scripps Research Institute, La Jolla, CA, 2003
  • BS, McGill University, Montreal, Quebec, 1998

Memberships

  • Member, “Drug Discovery, Delivery and Experimental Therapeutics” research program, University of Kansas Cancer Center, 2013-2016

Honors & Awards

  • Leading Light Award for research productivity, University of Kansas, 2013
  • Alfred P. Sloan Research Fellowship, 2010-2012
  • Damon Runyon Postdoctoral Fellowship, 2004-2007
  • Jairo H. Arevelo Fellowship, 2002-2003
  • La Jolla Interfaces in Science (Burroughs Wellcome Fund) Postgraduate Scholarship, 2001-2003
  • Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship, 2000-2002
Research Profile

Research Program

Research Interests

Modulating protein activity using small molecules

My lab builds novel chemical tools for modulating biological systems. We “design in” new ligand binding sites that allow us to selectively activate proteins, and we identify novel chemical inhibitors that allow us to disrupt protein activity. We are especially focused on:

  • Designing compounds that restore activity to cancer-associated p53 mutants
  • Building new therapeutic antibodies that can be selectively activated using small molecules
  • Designing inhibitors of RNA-binding proteins that contribute to cancer
  • Developing new approaches for rationally designing allosteric modulators of protein-protein interactions

Lab Overview

Lab Staff

Nan Bai

PhD student

Karen Khar

PhD student

Jake Khowsathit

PhD student

Shipra Malhotra

PhD student

Publications

Selected Publications

Gowthaman R*, Miller S*, Rogers S, Khowsathit J, Lan L, Bai N, Johnson DK, Liu C, Xu L, Anbanandam A, Aubé J, Roy A, Karanicolas J. “DARC: mapping surface topography by ray-casting for effective virtual screening at protein interaction sites” J. Med. Chem., 59, p. 4152-70 (2016).

Ali AM, Reis JM, Xia Y, Rashid AJ, Mercaldo V, Walters BJ, Brechun KE, Borisenko V, Josselyn SA, Karanicolas J, Woolley GA. “Optogenetic inhibitor of the transcription factor CREB” Chem. Biol., 22, p. 1531-9 (2015).

Johnson DK, Karanicolas J. “Selectivity by small-molecule inhibitors of protein interactions can be driven by protein surface fluctuations” PLOS Comput. Biol., 11, p. e1004081 (2015).

Xia Y, DiPrimio N, Keppel TR, Vo B, Fraser K, Battaile KP, Egan C, Bystroff C, Lovell S, Weis DD, Anderson JC, Karanicolas J. “The designability of protein switches by chemical rescue of structure: mechanisms of inactivation and reactivation” J. Amer. Chem. Soc., 135, p. 18840-9  (2013).

Gowthaman R, Deeds EJ, Karanicolas J. “Structural properties of non-traditional drug targets present new challenges for virtual screening” J. Chem. Inf. Model., 53, p. 2073-81 (2013).

Johnson DK, Karanicolas J. “Druggable protein interaction sites are more predisposed to surface pocket formation than the rest of the protein surface” PLOS Comput. Biol., 9, p. e1002951 (2013).

Deckert K, Budiardjo SJ, Brunner LC, Lovell S, and Karanicolas J. “Designing allosteric control into enzymes by chemical rescue of structure” J. Amer. Chem. Soc., 134, p. 10055-60  (2012).

Additional Publications

PubMed

This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
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