Born to Indian immigrant graduate student parents in Lafayette, Indiana in 1954, I grew up in Worcester, Massachusetts, received the BA degree from Swarthmore College in 1975, and did graduate work at The Rockefeller University in New York City. There, I had the privilege of being the first graduate student of Guenter Blobel (Nobel Laureate in Physiology and Medicine, 1999). My thesis research was on the signal hypothesis for nascent protein targeting to the endoplasmic reticulum, for which I received the PhD degree in 1979. I then completed the MD degree at Cornell University Medical College in 1980, and  internal medicine residency at the University of California, San Francisco (UCSF). I stayed on the faculty at UCSF as Professor of Physiology and Medicine engaged in basic research, medical student and resident teaching and training, and general internal medicine clinical practice, from 1982 until I left in 2004 to found Prosetta Biosciences, an early stage biotech company based in San Francisco, with subsidiaries in Seattle, WA and Mysuru, Karnataka, India. 

My academic research interests focused on biological regulation of protein biogenesis, culminating in the discovery and study of mechanisms by which protein folding was productively regulated to generate variable amounts of diverse functional forms of proteins, phenomena akin to what is today termed “protein moonlighting” (see for example, E. Alpert et al 2021). At UCSF we discovered a host-catalyzed pathway of viral capsid assembly, and at Prosetta we adapted those assays into moderate throughput phenotypic drug screens involving cell-free protein synthesis and assembly (CFPSA) systems. We identified over 300 structurally dissimilar small molecules we termed assembly modulators, by screening for the ability to modulate capsid formation in each of the families of virus known to cause serious human disease. They were the starting point for advancement to compounds, now validated in diverse animal models, for many therapeutic areas including many with previously unprecedented activities such as one drug for all respiratory viruses, one drug for all cancers, a drug efficacious against both familial and sporadic ALS, a drug active targeting mTOR that prevents alpha-synuclein aggregation, and a drug active against gram + and gram – bacteria, to name some highlights. The targets of these drugs are  allosteric sites on miniscule subsets of key protein components within different transient, energy-dependent multi-protein complexes that we term assembly machines. It appears that in diverse diseases the normal, healthy assembly machine is rendered aberrant, including dissociated from host defenses. The drugs we have advanced are ones that drive the aberrant assembly machine back to normal, with restoration of key proteins involved in host defense such as autophagy adaptor p62/SQSTM1, in a manner that is extremely difficult, if not impossible, for viruses (and bacteria) to develop resistance, unlike conventional drugs. Thus these assembly modulators appear to both stop the disease and restore homeostasis. We currently seek funding to advance these remarkable compounds to human clinical trials.