Jeffery W Kelly

Jeffery W. Kelly (born August 23, 1960 in Medina, New York) is the former Dean of Graduate Studies (2000-2008) and Vice President of Academic Affairs (2000-2006) and currently is the Chairman of Molecular Medicine and the Lita Annenberg Hazen Professor of Chemistry within the Skaggs Institute of Chemical Biology at The Scripps Research Institute in La Jolla, California. His research focuses on understanding protein folding, misfolding and aggregation and on developing both chemical and biological strategies to ameliorate diseases caused by protein misfolding and/or aggregation. Of the 100 Ph.D. students and postdoctoral fellows who have trained in the Kelly Lab., > 40 are in tenured or tenure-track academic jobs.

Kelly received his Ph.D. in organic chemistry from the University of North Carolina at Chapel Hill (1986) and performed post-doctoral research at The Rockefeller University (1986–89). His research focuses on the chemistry and biology of protein homeostasis or proteostasis. Besides studying the structural and energetic basis underlying protein folding, his laboratory also studies the etiology of neurodegenerative diseases linked to protein aggregation, including Alzheimer's disease, Parkinson's Disease, and the light chain, gelsolin and transthyretin-based amyloidoses–publishing over 320 peer-reviewed papers in this area to date (h-index = > 85; ISI Web of Science). He has also provided insight into genetic diseases associated with loss of protein function, such as the lysosomal storage diseases.

Kelly has cofounded three biotechnology companies, FoldRx Pharmaceuticals (with Susan Lindquist), now owned by Pfizer, Proteostasis Therapeutics, Inc. (with Andrew Dillin and Richard Morimoto) (a NASDAQ public company) and Misfolding Diagnostics (with Xin Jiang and Justin Chapman; a private corporation). The Kelly laboratory discovered the first regulatory agency-approved drug that slows the progression of a human amyloid disease using a structure-based design approach. This drug, now called Tafamidis or Vyndaqel, slowed the progression of familial amyloid polyneuropathy in an 18-month placebo controlled trial and in a 12-month extension study sponsored by FoldRx Pharmaceuticals (acquired by Pfizer in 2010). Vyndaqel or Tafamidis was approved for the treatment of Familial amyloid Polyneuropathy by the European Medicines Agency in late 2011 and subsequently has been approved in > 30 countries. A second statistically significant clinical trial with the repurposed Merck Non steroidal anti-inflammatory drug, diflunisal discovered by Kelly to kinetically stabilize TTR, confirms the validity of the kinetic stabilizer mechanism to ameliorate the TTR amyloidoses. Collectively, the tafamidis and diflunisal data provide compelling pharmacologic evidence supporting the amyloid hypothesis, the idea that active transthyretin aggregation causes the loss of post-mitotic tissue in this degenerative amyloid disease. Moreover, these data validate transthyretin as a key drug target to stop the progression of several degenerative phenotypes linked to transthyretin aggregation.

In addition to discovering the first drug that slows the progression of a human amyloid disease, the Kelly Laboratory is credited with demonstrating that transthyretin conformational changes alone are sufficient for amyloidogenesis, discovering the first example of functional amyloid in mammals, making major contributions toward understanding β-sheet folding, discovering the "enhanced aromatic sequon"–sequences that are more efficiently N-glycosylated by cells and which stabilize the native state of proteins that they are incorporated into as a consequence of aromatic side chain–N-glycan interactions and was corresponding author on and contributed some of the key experimental data demonstrating that altering cellular protein homeostasis or proteostasis capacity has the potential to alleviate protein misfolding and aggregation diseases.

Kelly was elected to the American Academy of Arts and Sciences in 2016, delivered the commencement address at SUNY Fredonia in 2016, and has won numerous awards including the American Institute of Chemists Chemical Pioneer Award, 2017; the Jacob Heskel Gabbay Award in Biotechnology and Medicine, 2016; the Royal Society of Chemistry Jeremy Knowles Award, 2016; the Biopolymers Murray Goodman Memorial Prize, 2012; the American Chemical Society, Ralph F. Hirschmann Award in Peptide Chemistry, 2012; the Protein Society Emil T. Kaiser Award, 2011; the American Peptide Society Rao Makineni Lectureship (Award), 2011; the American Peptide Society Vincent du Vigneaud Award, 2008; the National Institutes of Health Merit Award, 2006; the American Chemical Society Arthur C. Cope Scholar Award, 2001; the SUNY at Fredonia Alumni Distinguished Achievement Award, 2000; the SUNY at Fredonia Chemistry Dept. Alumni Award, 2000; the Protein Society-Dupont Young Investigator Award, 1999; the Biophysical Society National Lecturer (Award), 1999; and the Searle Scholar Award, 1991.