Category: Whitty, Adrian
Professor Whitty was awarded a 4 Year grant by the National Institute of Health (NIH) to further his studies of NF-kB Modulators. The title of the Research Project is: Structure and Mechanism of NF-kB Essential Modulator (NEMO).
This funding will allow Professor Whitty and his Co-PIs Professors Karen Allen of Chemistry and Thomas Gilmore of Biology to advance our understanding of the signaling scaffold protein NF-κB essential modulator (NEMO), a component of the inhibitor of κB kinase (IKK) complex, which is a key regulatory node for NF-κB signaling. In addition to NEMO playing a role in the chronic hyperactivity of NF-κB in human diseases, mutations in NEMO are found in several human immunodeficiency diseases. The long-term goals of the project are to understand how scaffolding proteins such as NEMO use conformational change to regulate the functional interactions between the signaling proteins that are bound to them, to elucidate the structural basis for disease-causing mutations in key regions of NEMO, and to identify new target sites for small molecule drugs that modulate NEMO activity.
Congratulations to Professors Whitty, Allen and Gilmore and their research team!
Half-day symposium on
«Macrocycles in Drug- and Agrochemical Discovery»
Tuesday, May 24, 2016, 13:30 – 17:45
Big Lecture Hall, Department of Chemistry
University of Basel, St. Johanns-Ring 19
This year’s annual symposium organized by the Division of Medicinal Chemistry & Chemical Biology of the Swiss Chemical Society is dedicated to the topic of Macrocycles in Drug- and Agrochemical Discovery.
This free event is gathering five globally renowned international experts in the field that will showcase the importance of this topic in drug discovery.
Dr. Whitty will start the day off with a discussion of his work on how proteins bind macrocycles. For more information on the event click here.
Professor Adrian Whitty has received a Templeton Award for Excellence in Student Advising in recognition of his strong and demonstrated commitment to the personal and academic development of his students. The award is presented each year at the College of Arts and Sciences Class Day ceremony.
In announcing the award, Dr. Steven Jarvi, Associate Dean for Student Academic Life, stated that the theme that emerged from the comments of Professor Whitty’s advisees is his sincerity and genuine interest in the well being of his students.
An international student commented that “he is from Europe, just like me, and he is interested in how my life is and how I’m adapting to America.” Another student mentioned that Professor Whitty “is the most kind-hearted and caring professor that I had the fortune to have class with.”
This 2011 award is the fourth time in a row that it has been conferred on a member of the Chemistry faculty. Previous winners have included, Sean Elliott (2008, an inaugural awardee), John Snyder (2009), and Binyomin Abrams (2010).
The Endowed Fund was established in 2008 with gifts from John and Josephine Templeton as a measure of their gratitude to the dedication shown by members of the Boston University faculty in the personal counseling, guidance, and advice they give to undergraduates.
Professor of Chemistry Karen Allen and Associate Professor of Chemistry Adrian Whitty gave a “Discoveries” talk to BU Alumni on December 1, 2010. Sponsored by the BU Alumni Association and the College of Arts & Sciences, the Discoveries lecture series taps the strength of BU faculty to give alumni a deeper look into the world and their lives.
The seminar, Lessons to be Learned from Cells: From Molecular Basis to Disease, highlighted advances and obstacles in current drug discovery and described how work at Boston University on NEMO, a protein in the pathways involved in human inflammatory diseases and cancers, aims to address critical problems.
There are many medically important drug targets that current drug discovery technology is not able to address. Collaborative basic research in Chemistry, Biology, and Biochemistry is key to solving these intractable problems to enable the discovery of new classes of drugs. A multidisciplinary team at Boston University, led by Associate Professor of Chemistry Adrian Whitty, aims to develop new approaches for challenging molecular targets. The National Institute of General Medical Sciences awarded this team a 4-year, $1.6 million grant entitled Design of Macrocyclic Inhibitors of the NEMO/IKKα/β Protein-Protein Interaction.
Only about 10% of the potential drug targets in the human genome have been successfully targeted with marketed drugs. Of the remaining 90%, many are intracellular proteins whose function is critically dependent on their reversible interactions with other proteins. Despite decades of effort by the pharmaceutical industry, developing oral drugs that inhibit protein-protein interactions (PPIs) has rarely succeeded and has become recognized as a major scientific and technological challenge.
The primary goal of this project is to determine whether the use of a class of natural product-inspired compounds called macrocycles constitutes a broadly applicable method for developing oral drugs against PPI targets. As a first challenge, the team is attempting to develop macrocycles that block the activity of NEMO, a key component of the IKK complex that activates NF-κB signaling. Chronic hyperactivity of the NF-κB pathway is associated with many human inflammatory diseases and cancers. Thus, the development of drug-like inhibitors of this pathway is highly relevant to public health.
The work will determine whether appropriately designed synthetic macrocycles can inhibit PPI targets while maintaining good drug-like properties. In terms of NF-κB and disease, their work will provide a means for testing whether inhibiting the interaction of NEMO with IKK—as a more targeted alternative to completely ablating all IKK activity—represents a useful new approach for attenuating inflammation.
In addition to Professor Whitty (quantitative biochemistry and drug discovery), the multidisciplinary research team comprises Professors Sandor Vajda and Dima Kozakov (computational chemistry), John Porco and Aaron Beeler (macrocycle synthesis), Karen Allen (X-ray crystallography), and Tom Gilmore (NF-κB pathway biology).
Adrian Whitty and group receive NIH Award to perform quantitative analysis of RET Receptor activation and signaling
The Whitty Group has received a 5-year, $2 million award from the NIH. Growth factors (GFs) are messenger proteins that mediate the signals between cells that regulate critical functions such as cell growth, maturation, and death. In comparison with other medicinally important protein classes (enzymes, ion channels and G protein-coupled receptors) little is known about how GF receptors perform their function. This project aims to address this important knowledge gap by using the GF receptor RET, which is important in sustaining the survival of a key population of nerve cells in the spinal cord, as a model system to elucidate how GF/GF receptor interactions are coupled to intracellular signaling and to the resulting cellular response. If successful, the new knowledge and experimental methods it will deliver will contribute to innovative and improved approaches to discovering and developing drugs that target GFs and their receptors.
Prof. Whitty received his undergraduate degree (B.Sc., Hon.) in Chemistry at King’s College, University of London in 1985, and his Ph.D. in Organic Chemistry from the University of Illinois at Chicago in 1991 working with Professor Paul Young. Following postdoctoral research with Professor William P. Jencks at Brandeis University in the field of Enzymology, Adrian joined Biogen Inc. (now Biogen Idec) in Cambridge, MA as staff scientist, where over 14 years he rose to the position of Director in the Drug Discovery Department and Head of Physical Biochemistry. In these roles he led a large group of research scientists employing structural biology, biochemistry, biophysics and computational approaches to investigate the mechanisms of action of potential drug targets and drug candidates, including both ‘biopharmaceutical’ (i.e. protein) and ‘small molecule’ (i.e. synthetic organic) drug discovery projects. Adrian additionally led or co-led project teams aimed at discovering drugs against specific drug targets. In his time at Biogen Idec Adrian was a highly productive research scientist with an excellent record of scientific publications. At the same time he engaged in impressive and focused mentoring of post-doctoral scholars. For several years he served as Director of the Biogen Idec Postdoctoral Program, and was cited by Science as one of the top postdoctoral mentors in the country (“Success factors for Postdocs,” September 17, 2004).