Shaeri Mukherjee, PhD, a cell biologist at UC San Francisco, has won the 2023 Bowes Biomedical Investigator award. The coveted prize, made possible by philanthropic support from the William K. Bowes Jr. Foundation, will provide her with unrestricted funding of $1.25 million over five years to further her pioneering work using bacterial pathogens to identify basic processes inside human cells.
"I feel enormous gratitude," said Mukherjee, an associate professor in the Department of Microbiology and Immunology and a member of the George Williams Hooper Research Foundation, an organized unit within the UCSF School of Medicine. "This award gives me the freedom to try out my craziest, wildest ideas that I think will make an impact but that I wouldn't be able to pursue otherwise."
Mukherjee's scientific boldness and creativity have led her to surprising revelations about the inner workings of mammalian cells, which have important implications for human health and disease. In 2007, for instance, as she was completing her doctoral degree, she became fascinated by Legionella pneumophila, a species of bacteria that causes a severe form of pneumonia called Legionnaires' disease. A lab at Yale University had found that when Legionella infects human cells, it secretes an enzyme that can rapidly fragment the Golgi apparatus, the hub for protein packaging and transport within a cell.
"I wanted to know how this bacterium does that," Mukherjee recalled. So, she joined the Yale lab as a postdoctoral fellow to find out. And her curiosity paid off.
In a 2013 paper, published in the prestigious journal Nature, she and her colleagues showed that Legionella makes a previously unknown type of modification to a particular Golgi protein that causes the apparatus to collapse. Interestingly, the same bacterial enzyme structure responsible for this modification is also present in a human protein known as huntingtin-yeast interacting protein E (HYPE), which is thought to play a role in Parkinson's disease, a neurodegenerative disorder.
This unexpected discovery convinced Mukherjee that Legionella and other pathogens can provide keys to unlock the mysteries of the cells they infect. "These bugs are really smart," she explained. "They manipulate our cells and use our own proteins against us." She decided she wanted to devote her career to studying the tiny, clever invaders as "a lens" to understand how human cells work.
There was just one problem: The research grant that employed her at Yale had run out, and Mukherjee, a citizen of India who was in the U.S. on a temporary visa, faced the prospect of having to return to her home country. "Research opportunities in India are limited compared to the U.S.," she lamented. "I was certain that my dream of doing cutting-edge science was gone."
But in July 2013, after she had presented her postdoctoral work at a conference, a renowned UCSF cell biologist named Peter Walter, PhD, introduced himself and encouraged her to apply for an open faculty position at UCSF. Mukherjee put together an application package that night. Two weeks later, she flew to San Francisco for a visit.
One of her interviewers was J. Michael Bishop, MD, a former UCSF chancellor and the director of the Hooper Foundation. In 1989, Bishop won a Nobel Prize for uncovering the genetic underpinnings of cancer using a chicken virus. He told Mukherjee, "I have great expectations for you because I had the same philosophy that viruses and bacteria can become excellent tools," she recalled. "They might lead you to something unexpected," he'd said. Mukherjee was hired at UCSF that fall.
She exemplifies what UCSF is all about. That includes outstanding science that is multidisciplinary and collaborative, and a strong devotion to mentorship.
"Shaeri is truly at the forefront of her field," said Mukherjee's department chair, Lewis Lanier, PhD, the J. Michael Bishop, MD, Distinguished Professor of Microbiology and Immunology. "She's extraordinarily innovative, she asks hard questions of medical importance, and her students love her."
"She exemplifies what UCSF is all about," said Joseph Bondy-Denomy, PhD, a fellow Bowes Biomedical Investigator and an associate professor in the Department of Microbiology and Immunology. "That includes outstanding science that is multidisciplinary and collaborative, and a strong devotion to mentorship." In addition to supporting Mukherjee's groundbreaking research, the Bowes award will allow her to help advance the careers of young scientists in her lab by funding their work on projects not covered by restrictive grants.
Going for Major Discoveries
UCSF launched the Bowes Biomedical Investigator Program in 2016 with a $50 million gift from the late William K. Bowes Jr., a venture capitalist who gave nearly $100 million to the university during his lifetime. The program supports basic scientists at the beginning or middle of their careers who take novel approaches to discovery and who have the potential to make significant contributions to biomedicine. These bold, curiosity-driven thinkers often follow unconventional paths such as combining disciplines or breaking open new fields, which makes their work difficult to fund through traditional means like grants from the National Institutes of Health (NIH).
"When you apply for an NIH grant, you have to already have done half of your experiments before you even have a chance of getting your study funded," Lanier said. "Where do you get the money for those early experiments? Having unrestricted resources like the Bowes award allows our scientists to go out on a limb and do really novel things."
"It's about validation," Bondy-Denomy added. "A Bowes award says, 'Hey, what you're doing belongs here, and you belong here. Keep up the good work.'"
Mukherjee is the fifth investigator named to the Bowes program. Past award recipients include Edward Chang, MD '04, the Joan and Sanford Weill Chair of Neurological Surgery and the Jeanne Robertson Distinguished Professor of Psychiatry; James Fraser, PhD, a professor in the Department of Bioengineering and Therapeutic Sciences; Danica Fujimori, PhD, the Stuart Lindsay Professor of Experimental Pathology IV in the Department of Cellular and Molecular Pharmacology; and Bondy-Denomy.
The Bowes awards are already enabling extraordinary breakthroughs. In 2021, for instance, Chang and his team announced the development of a "speech prosthesis" that can translate brain signals from a paralyzed man into words on a computer screen. Fraser's work studying the shapes and movements of macromolecules, meanwhile, helped garner a $67.5 million grant from the National Institute of Allergy and Infectious Diseases to create new antiviral therapies for COVID-19 and other viral diseases - the largest grant in UCSF history.
Mukherjee plans to use her award to continue exploring crucial cell functions with the help of their bacterial nemeses. Recently, her lab found that a toxin made by Legionella mimics tRNA, a molecule that facilitates protein production. "We can use this toxin to understand protein synthesis and other related cellular processes," she said.
She recalled something Walter once told her. "Life is short," he'd said. "Do not waste your time on unimportant experiments. Go for the major discoveries. It may take a lot of effort, and you may fail, but what you do will be meaningful."
"That has always been my guiding light," Mukherjee said.
