Adrian Whitty, PhD
Associate Professor
Boston University College of Arts and Sciences
Dept of Chemistry

PhD, University of Illinois, Chicago
MS, University of Illinois, Chicago

Professor Whitty received his Ph.D. in Organic Chemistry in 1991 from the University of Illinois at Chicago, followed by postdoctoral work with William P. Jencks at Brandeis University. Prior to joining the Boston University faculty in 2008, Adrian Whitty worked for 14 years at Biogen Idec (then Biogen Inc.). He rose from staff Scientist to the position of Director in the Drug Discovery Department and Head of Physical Biochemistry, leading a department that encompassed Quantitative Biochemistry, Assay Development and Compound Profiling, Structural Biology, and Molecular Modeling. During his time at Biogen Idec Prof. Whitty participated in or led multiple drug discovery project teams. He also maintained an active research program in the areas of receptor signaling and protein-ligand binding. He additionally directed the Biogen Idec Postdoctoral Program, developing a sterling reputation as a post-doctoral mentor.

The Whitty Group studies protein-protein and protein-ligand recognition, with an emphasis on how binding energy from these intermolecular interactions can be utilized to achieve biological function or inhibition. We apply this research in two distinct areas: (i) developing a quantitative, mechanistic understanding of the activation and signaling of growth factor receptors, and (ii) advancing our ability to discover drugs that inhibit protein-protein interactions.

Activation and signaling mechanisms in growth factor receptor systems: This work aims to address longstanding mechanistic questions concerning exactly how the binding of a cytokine or growth factor brings about an activated state of its receptor, and how the assembly of the activated receptor complex is quantitatively coupled to proximal and distal signaling events and to the ultimate cellular response (See Schlee et al., Nature Chemical Biology, 2006).

Discovery and characterization of small molecule (i.e. synthetic organic) inhibitors of protein-protein interactions: We aim to develop new approaches to this difficult problem, based on achieving a better understanding of what structural and physicochemical properties at protein-protein interfaces are important for inhibitor binding, and what kinds of novel chemical structures are best suited to exploit these features. Projects in this area are carried out in collaboration multiple other groups encompassing computational chemistry (Prof. Vajda), organic synthesis (Profs. Porco, Beeler, CMLD-BU; Prof. Pollastri, Northeastern U.), X-ray crystallography (Prof. Allen) and Biology (Prof. Gilmore, BU Department of Biology).

Techniques & Resources:

Development and implementation of biochemical and cell-based assays using state-of-the art technologies such as FRET, Time-Resolved Fluorescence, and Fluorescence Polarization.

Biophysical methods – the lab is equipped with a Biacore 3000 surface plasmon resonance (SPR) instrument for measuring protein-ligand binding in real time. Other biophysical methods used include fluorescence, analytical ultracentrifugation (AUC), dynamic lightscattering (DLS) and isothermal titration calorimetry (ITC).

Mammalian Cell Culture – the lab has a dedicated Tissue Culture facility equipped with laminar flow biosafety cabinet, cell incubators, centrifuge, Nikon inverted microscope, and liquid nitrogen cell storage system.

Specialized techniques for cell analysis (e.g. flow cytometry using a Becton-Dickinson FACSCaliburTM)

Quantitative data analysis, curve fitting and reaction pathway modeling using a variety of software packages including site licenses to MathematicaTM and MatLab®.

Molecular Mechanism of the NFkappaB Essential Modulator (NEMO) Scaffold Protein Mutated in Human Immunodeficiencies
08/15/2016 - 06/30/2020 (PI)
NIH/National Institute of General Medical Sciences

Generation of Reporter Gene Cell Line for Neublastin (NBN)
01/01/2014 - 06/11/2019 (PI)
Biogen Idec

Activation and Signaling Mechanism of the RET Tyrosine Kinase Receptor (NRSA Fellowship for Jennifer Chow)
09/12/2016 - 09/11/2017 (PI)
NIH/National Cancer Institute

Activation and Signaling Mechanism of the RET Tyrosine Kinase Receptor (NRSA Fellowship for Jennifer Chow)
09/12/2013 - 09/11/2016 (PI)
NIH/National Cancer Institute

Software for Fragment Based Design of Covalent Inhibitors
09/10/2014 - 09/09/2016 (PI)
Acpharis, Inc. NIH NIGMS

Discovery of Small Molecule Drug Candidates That Disrupt the NEMO/IKK Signaling Complex
08/05/2013 - 07/31/2016 (PI)
Carmot Therapeutics, Inc. NIH NCI

Design of Macrocyclic Inhibitors of the NEMO/IKKa/b Protein-Protein Interaction
09/01/2010 - 07/31/2016 (PI)
NIH/National Institute of General Medical Sciences

01/01/2010 - 01/31/2015 (PI)
NIH/National Institute of General Medical Sciences

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Vajda S, Beglov D, Wakefield AE, Egbert M, Whitty A. Cryptic binding sites on proteins: definition, detection, and druggability. Curr Opin Chem Biol. 2018 May 22; 44:1-8. PMID: 29800865.
  2. Beglov D, Hall DR, Wakefield AE, Luo L, Allen KN, Kozakov D, Whitty A, Vajda S. Exploring the structural origins of cryptic sites on proteins. Proc Natl Acad Sci U S A. 2018 Apr 10; 115(15):E3416-E3425. PMID: 29581267.
  3. Whitty A, Viarengo LA, Zhong M. Progress towards the broad use of non-peptide synthetic macrocycles in drug discovery. Org Biomol Chem. 2017 Sep 26; 15(37):7729-7735. PMID: 28876025.
  4. Whitty A, Zhong M, Viarengo L, Beglov D, Hall DR, Vajda S. Quantifying the chameleonic properties of macrocycles and other high-molecular-weight drugs. Drug Discov Today. 2016 May; 21(5):712-7. PMID: 26891978; DOI: 10.1016/j.drudis.2016.02.005;.
  5. Hall DR, Kozakov D, Whitty A, Vajda S. Lessons from Hot Spot Analysis for Fragment-Based Drug Discovery. Trends Pharmacol Sci. 2015 Nov; 36(11):724-36. PMID: 26538314; PMCID: PMC4640985; DOI: 10.1016/;.
  6. Kozakov D, Hall DR, Napoleon RL, Yueh C, Whitty A, Vajda S. New Frontiers in Druggability. J Med Chem. 2015 Dec 10; 58(23):9063-88. PMID: 26230724; PMCID: PMC4762776; DOI: 10.1021/acs.jmedchem.5b00586;.
  7. Vajda S, Whitty A, Kozakov D. Fragments and hot spots in drug discovery. Oncotarget. 2015 Aug 7; 6(22):18740-1. PMID: 26300051; PMCID: PMC4662450.
  8. Whitty A. A Particularly Discriminating Receptor. Cell Syst. 2015 Jul 29; 1(1):14-5. PMID: 27135685; DOI: 10.1016/j.cels.2015.07.004;.
  9. Kozakov D, Hall DR, Jehle S, Jehle S, Luo L, Ochiana SO, Jones EV, Pollastri M, Allen KN, Whitty A, Vajda S. Ligand deconstruction: Why some fragment binding positions are conserved and others are not. Proc Natl Acad Sci U S A. 2015 May 19; 112(20):E2585-94.View Related Profiles. PMID: 25918377; PMCID: PMC4443342; DOI: 10.1073/pnas.1501567112;.
  10. Yeo AT, Chennamadhavuni S, Whitty A, Porco JA, Gilmore TD. Inhibition of Oncogenic Transcription Factor REL by the Natural Product Derivative Calafianin Monomer 101 Induces Proliferation Arrest and Apoptosis in Human B-Lymphoma Cell Lines. Molecules. 2015; 20(5):7474-94.View Related Profiles. PMID: 25915462; PMCID: PMC4863944; DOI: 10.3390/molecules20057474;.
Showing 10 of 66 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 66 publications over 22 distinct years, with a maximum of 8 publications in 2015

Contact for Mentoring:

590 Commonwealth Ave
Boston MA 02215
Google Map

(617) 353-6466 (fax)

Whitty's Networks
Click the "See All" links for more information and interactive visualizations
Similar People
Same Department