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®.


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

Molecular Mechanism of the NFkappaB Essential Modulator (NEMO) Scaffold Protein Mutated in Human Immunodeficiencies
08/15/2016 - 06/30/2018 (PI)
NIH/National Institute of General Medica
1R01GM117350-01A1

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
4F31CA177224-04

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
5F31CA177224-03

Software for Fragment Based Design of Covalent Inhibitors
09/10/2014 - 09/09/2016 (PI)
Acpharis, Inc. NIH NIGMS
1R43GM109555-01A1

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
5R44CA153676-03

Design of Macrocyclic Inhibitors of the NEMO/IKKa/b Protein-Protein Interaction
09/01/2010 - 07/31/2016 (PI)
NIH/National Institute of General Medica
5R01GM094551-04

QUANTITATIVE ANALYSIS OF RET RECEPTOR ACTIVATION AND SIGNALING
01/01/2010 - 01/31/2015 (PI)
NIH/National Institute of General Medica
5R01GM087469-04



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. 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/j.tips.2015.08.003;.
  2. 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;.
  3. 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.
  4. 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;.
  5. 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;.
  6. 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;.
  7. Li S, Bhave D, Chow JM, Riera TV, Schlee S, Rauch S, Atanasova M, Cate RL, Whitty A. Quantitative analysis of receptor tyrosine kinase-effector coupling at functionally relevant stimulus levels. J Biol Chem. 2015 Apr 17; 290(16):10018-36. PMID: 25635057; PMCID: PMC4400318; DOI: 10.1074/jbc.M114.602268;.
  8. Whitty A, Zhou L. Horses for courses: reaching outside drug-like chemical space for inhibitors of challenging drug targets. Future Med Chem. 2015; 7(9):1093-5. PMID: 26132520; DOI: 10.4155/fmc.15.56;.
  9. Zhou L, Yeo AT, Ballarano C, Weber U, Allen KN, Gilmore TD, Whitty A. Disulfide-mediated stabilization of the I?B kinase binding domain of NF-?B essential modulator (NEMO). Biochemistry. 2014 Dec 23; 53(50):7929-44.View Related Profiles. PMID: 25400026; PMCID: PMC4278678; DOI: 10.1021/bi500920n;.
  10. Villar EA, Beglov D, Chennamadhavuni S, Porco JA, Kozakov D, Vajda S, Whitty A. How proteins bind macrocycles. Nat Chem Biol. 2014 Sep; 10(9):723-31.View Related Profiles. PMID: 25038790; PMCID: PMC4417626; DOI: 10.1038/nchembio.1584;.
Showing 10 of 62 results. Show More

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

Bar chart showing 62 publications over 19 distinct years, with a maximum of 8 publications in 2015

YearPublications
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