People

Pradipta Ghosh, MD

Taking the first steps: Those who knew Pradipta as a child would agree that she is easily bored if not constantly challenged. Building a knowledge base that is very broad and deep was her way to take on the challenge in exploring anything that she knew little or nothing about. After graduating as the Best Outgoing Student in a nationwide ranking, from the top medical school in India, Pradipta came to US in 2001 in search of the next challenge, that of a career in biomedical science. This twist in career was prompted by a famous quote that she had stumbled upon -- "Medicine is not only an art; it is also a science. It does not consist of compounding pills and plasters; it deals with the very processes of life, which must be understood before they may be guided". Determined to get trained in a good laboratory, she applied to Universities in US with little or no hope of hearing back. Her dream materialized when her resume trickled through the system and fell in the hands of Stuart Kornfeld at Washington University St Louis, MO, a seasoned physician-scientist and a great mentor, an astute judge of character and talent, who agreed to give Pradipta an opportunity to train in his laboratory. Pradipta was quick to realize that this rare opportunity comes with extraordinary challenges ahead because she was about to enter a dual-career path, that of a physician-scientist, with no prior training as a scientist and years of rigorous internship, residency and fellowship in US ahead of her. She was introduced to experimental medicine in the Kornfeld laboratory, where she took the very first steps in her scientific career. Soon her vocation became her passion and what followed during the next 18 months was nothing short of magic. Her work investigated how adaptor proteins, GGAs and AP1&2, affected sorting of Mannose-6 Phosphate Receptors (MPRs) and directly led to the discovery of a layer of complexity in the multi-step sorting of the receptor in-and-out of the Golgi. Through her publications within the next year, a novel paradigm emerged in the field of protein trafficking where series of ying-yang phospho- and dephosphorylation events regulate each step of receptor trafficking based on the temporospatial distribution of the respective kinases or phosphatases. If St Louis winters were cold, or summers hot, Pradipta would not know because she was in the lab round-the-clock acquiring the scientific tools and building her technical expertise. She recalls that the learning curve was steep, but she enjoyed every moment of the journey, gaining unique perspective and broadening her horizon with every passing day. She describes her time spent in the Kornfeld lab as the most formative years of her scientific career because it served as a solid foundation for the years to come.

Building on the foundation: In 2003, Pradipta moved to the University of California, San Diego (UCSD) to begin her clinical training in Internal Medicine. After fast-tracking through her internship and residency in the physician-scientist training pathway, she joined the UC San Diego Gastroenterology Fellowship Program in 2005. A year later, she began her postdoctoral research training in the George Palade laboratories under the mentorship of Dr. Marilyn G. Farquhar, PhD Equipped with the skills of a biochemist, this is where she honed her skills as a cellular and molecular biologist, and further broadened her horizon by incorporating systems biology, computational modeling and bioinformatics into her research program. Her postdoctoral work on a newly discovered protein, GIV/Girdin, established the presence of a novel class of signaling molecules and unraveled hitherto unknown functions of these molecules in cell biology and pathophysiology. In 2008 she graduated from the Gastroenterology fellowship program and joined as an Assistant Professor on tenure track in the department of Medicine at UC San Diego. Ongoing work in her laboratory seeks to identify novel signal amplifiers (a new class of molecules that she christened GEMs, guanine nucleotide exchange modulators) in a systematic and unbiased way using a three-pronged approach. Using these approaches her laboratory has already identified new rheostats with surprising functions during cellular processes such as membrane-trafficking, autophagy, survival, apoptosis, mitosis, differentiation and migration. Once systematically applied, these approaches have the real potential to revolutionize our understanding of signal transduction and the diverse biological processes and disease states that they control. 

Emergence of a new paradigm: Pradipta's group was one of the original discoverers of this GEM signaling system beginning with the discovery of GIV-GEM, and subsequently extending to 3 other members such as NUCB1/2 and Daple-GEMs. We showed that GEMs serve as vital platforms for intracellular communication networks; they coordinate cellular responses and organellar function in cells responding to environmental signals initiated by diverse classes of receptors, thereby allowing non-GPCRs to engage with and modulate trimeric-GTPases. Using the powerful synergy of cell, molecular and structural-biology, molecular imaging, systems biology and bioinformatics, her group showed the crucial importance of the GEM system in coordinating diverse cellular processes and revealed the mechanistic basis of their GEM action. As a physician-scientist, she relentlessly pursued why/how aberrations in the GEM system spur diseases such as cancer progression, fibrosis and insulin resistance and provided impetus to developdrugs targeting the GEMs in disease states.

This paradigm of intracellular GTPase signaling that is modulated by GEMs is strikingly different from how trimeric-GTPases were previously believed to function in cells. Published and ongoing molecular, structural and systems biology, and molecular imaging studies spearheaded by her lab have confirmed this paradigm and revealed its importance in diseases such as cancers, fibrosis and diabetes. These studies showed that the GEM-GTPase system doesn't just transduce signals; rather, like the Internet communication protocols which link devices worldwide, they serve as network-protocols for intracellular communication at diverse intracellular microdomains. GEMs route signals between organelles and facilitate communication with the cell's exterior.

The leap into the unknown where science led: In launching the Institute for Network Medicine (iNetMed), Pradipta's goal is to not only reveal the importance of GEMs in health and diseases, but also unravel other molecules like GEMs that support a complete system of network-protocols for cellular communication; in short, she seeks to decode the cell's communication network using a transdisciplinary team-based approach, the Consortium for Cell-Inspired Systems Engineering (ConCISE). The iNetMed also supports the complete pipeline for network-based target identification and validation through our own Center for Precision Computational Systems Network (PreCSN) initiative and the HUMANOID™ Center of Research Excellence (CoRE), a center dedicated to building human organoid-based disease models. While network-based drug discovery can offer precision in targeting, HUMANOID allows personalized disease-modeling platforms for drug screening. Pradipta's overall vision is to drive disruptive research in biology, medicine and engineering using the fundamentals of network biology, systems engineering and medicine, with the ultimate goal of enhancing, enriching and improving human existence.

Come discover with the gang! Pradipta's laboratory has experience and expertise in most cell biological and translational approaches, including live cell imaging, designing and working with FRET probes, protein purification and analysis, protein-protein interaction assays, biochemical and pharmacological assays and in the use of animal models. Pradipta has had a successful training record at UCSD, mentoring several undergraduate, predoctoral students, and postdoctoral associates. 

As recently as April 2021, Pradipta withdrew from all clinical services to devote 100% of her effort to her research programs. Prior to that, every Friday morning, she used to see patients in a subspeciality outpatient clinic (Hepatology) or performs procedures in endoscopy suits at the VA Medical Center, La Jolla. 

Pradipta's Research Mentors:

• (August 2001 - May 2003): Stuart A. Kornfeld, MD (Washington U in St. Louis, MO)
  
• (September 2006 - November 2008): Marilyn G. Farquhar, PhD (UC San Diego, CA)
  

Professional Experience: 

Awards & Honors