Bhatt’s search for answers led her to the laboratory, where she used genomics to understand the diseases that had presented in those bone marrow transplantation patients. Her investigation led to an important discovery—the genome of a new bacterium—and set the stage for her current research. “That’s the moment when my eyes started to open. I realized that there are many more types of bacteria and viruses and fungi that live within us, in our microbiome, than we know about.”

As a child, Ami Bhatt, MD, PhD (assistant professor, Hematology, and assistant professor, Genetics), found herself drawn to science. “I was always curious, and I wanted to apply my curiosity in a way that could help people,” she recalls. These dual instincts led her to medicine, where she found her calling as a physician-scientist. Today Bhatt runs her own laboratory at Stanford, where she studies how shifts in the microbiome—the vast community of bacteria and other microscopic life that live on the body—affect human disease and patient outcomes.

Bhatt first became interested in the intersection of infection and malignancy as a medical student at UCSF. “At UCSF I saw a lot of patients with HIV who died of opportunistic infections,” she explains.  Several years later she encountered a similar trend while on rotation for Brigham and Women’s Hospital’s bone marrow transplantation service.  “A lot of the bone marrow transplant patients were getting sick with syndromes that seemed like infections, but we weren’t able to identify the infectious triggers because we didn’t know what we were looking for.”

Bhatt’s search for answers led her to the laboratory, where she used genomics to understand the diseases that had presented in those bone marrow transplantation patients. Her investigation led to an important discovery—the genome of a new bacterium—and set the stage for her current research. “That’s the moment when my eyes started to open. I realized that there are many more types of bacteria and viruses and fungi that live within us, in our microbiome, than we know about.”

Bhatt and her colleagues use cutting-edge genetic sequencing technologies and a sophisticated understanding of diseases to try to “solve mysteries that occur in immunocompromised patients. The fundamental thesis that drives our research,” she explains, “is that patient outcomes are manipulated or modified by the alterations in their microbiota, and that we can discover these microbes using sequence-based technologies.” Once the microbes are identified, Bhatt’s team works to clarify the mechanistic underpinnings of the microbiota-disease relationship. This information is then used to alter the microbiota through targeted drugs or treatments.

Another of Bhatt’s initiatives aims to unravel a particularly interesting question: What molecular changes occur during a fecal microbiota transfer? To answer this, Bhatt and her colleagues have developed a computational pipeline that will provide a time-based characterization of what actually happens during a transfer.

While her research goals are ambitious and varied, the source of Bhatt’s passion remains the same. “I’m still committed to the idea of being able to help people using science,” she says. “It’s been exciting to see our lab grow from just me in an empty room to a vibrant, interactive environment. We currently have eight talented staff members from all over the world. It’s a fun and bustling place. I feel like I am one of those lucky few who get to do exactly what they want to do.”

Bhatt’s search for answers led her to the laboratory, where she used genomics to understand the diseases that had presented in those bone marrow transplantation patients. Her investigation led to an important discovery—the genome of a new bacterium—and set the stage for her current research. “That’s the moment when my eyes started to open. I realized that there are many more types of bacteria and viruses and fungi that live within us, in our microbiome, than we know about.”

Bhatt and her colleagues use cutting-edge genetic sequencing technologies and a sophisticated understanding of diseases to try to “solve mysteries that occur in immunocompromised patients. The fundamental thesis that drives our research,” she explains, “is that patient outcomes are manipulated or modified by the alterations in their microbiota, and that we can discover these microbes using sequence-based technologies.” Once the microbes are identified, Bhatt’s team works to clarify the mechanistic underpinnings of the microbiota-disease relationship. This information is then used to alter the microbiota through targeted drugs or treatments.

Another of Bhatt’s initiatives aims to unravel a particularly interesting question: What molecular changes occur during a fecal microbiota transfer? To answer this, Bhatt and her colleagues have developed a computational pipeline that will provide a time-based characterization of what actually happens during a transfer.

While her research goals are ambitious and varied, the source of Bhatt’s passion remains the same. “I’m still committed to the idea of being able to help people using science,” she says. “It’s been exciting to see our lab grow from just me in an empty room to a vibrant, interactive environment. We currently have eight talented staff members from all over the world. It’s a fun and bustling place. I feel like I am one of those lucky few who get to do exactly what they want to do.”

Levy and his colleagues wondered what would happen when they combined drugs based on these two approaches. While immune therapies are only effective in some patients, they can lead to long-term remissions. Targeted therapies, on the other hand, usually cause short-term improvements, but work in more patients.

“We thought that putting the two together had the potential to get the best of both worlds,” says Levy.

So the team launched a preclinical study using anti-PD-L1 antibodies, an immunotherapy, together with the targeted drug ibrutinib.

Both of these drugs have been approved by the FDA and are actively being used in the clinic now. Together, the drugs were even more effective.

For decades, scientists have diligently been working toward new treatments for cancers by pursuing two lines of research: harnessing the power of the immune system to seek out and destroy tumors, or suffocating the tumors by blocking molecular pathways vital to the cancers’ survival. The best way to cure a cancer, though, may involve combining these two lines of attack, according to new research led by Stanford oncologist Ronald Levy, MD (professor, Oncology).

“Individually, these two kinds of therapies are already changing our cancer therapy paradigm,” says Levy. “But when combined, I think they’re really going to change things.”

The idea behind so-called cancer immunotherapies is that the human body already has built-in defenses that can abolish foreign entities; just as the immune system can fight off a cold virus, many researchers theorize that it can be coaxed to fight off a cancer. In the past few years, drugs based on this idea—which boost the activity of the immune system or trick it into attacking cancer cells—have begun to hit the market.

At the same time, targeted therapeutics are emerging that take advantage of the growing knowledge that scientists have gained about the genetics of cancers. When studies discover a particular mutation in a cancer cell’s DNA that allows it to thrive, researchers can develop drugs that reverse the effects of the mutation, stopping a cancer’s growth in its tracks.

Levy and his colleagues wondered what would happen when they combined drugs based on these two approaches. While immune therapies are only effective in some patients, they can lead to long-term remissions. Targeted therapies, on the other hand, usually cause short-term improvements, but work in more patients.

“We thought that putting the two together had the potential to get the best of both worlds,” says Levy.

So the team launched a preclinical study using anti-PD-L1 antibodies, an immunotherapy, together with the targeted drug ibrutinib.

Both of these drugs have been approved by the FDA and are actively being used in the clinic now. Together, the drugs were even more effective.

In mice with lymphomas, breast cancers, and colon cancers, the combination of anti-PD-L1 and ibrutinib shrank tumors and cured the animals. The therapies were revving up the immune system’s T cells to successfully destroy existing cancer cells. Even in cancers that didn’t respond to either drug alone, the combination yielded positive results. Moreover, the drug combination successfully taught the animals’ immune systems how to fight off the cancers in the future: when new cancer cells were injected into the mice after their original tumor had disappeared, they successfully destroyed the cells before they formed a new tumor.

“It seems that what some people have been hypothesizing all these years—that the immune system is ready to attack cancers if we give it a nudge—is completely true,” Levy says.

Now, the Stanford team is collaborating with the companies that produce anti-PD-L1 antibodies and ibrutinib to launch clinical trials of the drug combination in humans; seven trials are already in progress, including two that will be based at Stanford.

“I think this is the future of cancer therapy,” says Levy. “I hope this will allow us to replace chemotherapy and all those bad side effects that they cause.”

In mice with lymphomas, breast cancers, and colon cancers, the combination of anti-PD-L1 and ibrutinib shrank tumors and cured the animals. The therapies were revving up the immune system’s T cells to successfully destroy existing cancer cells. Even in cancers that didn’t respond to either drug alone, the combination yielded positive results. Moreover, the drug combination successfully taught the animals’ immune systems how to fight off the cancers in the future: when new cancer cells were injected into the mice after their original tumor had disappeared, they successfully destroyed the cells before they formed a new tumor.

“It seems that what some people have been hypothesizing all these years—that the immune system is ready to attack cancers if we give it a nudge—is completely true,” Levy says.

Now, the Stanford team is collaborating with the companies that produce anti-PD-L1 antibodies and ibrutinib to launch clinical trials of the drug combination in humans; seven trials are already in progress, including two that will be based at Stanford.

“I think this is the future of cancer therapy,” says Levy. “I hope this will allow us to replace chemotherapy and all those bad side effects that they cause.”

WELL will engage tens of thousands of volunteers—called “citizen scientists”—in two initial locations: Santa Clara County, California, and Hangzhou, China, with plans to expand to other sites as additional funding is secured. The citizen scientists participating in this effort will contribute information to improve our understanding of what makes lives healthier.

Santa Clara County was selected because it is one of the most diverse counties in the United States and is home to people of many cultures and income levels. This diversity provides unique opportunities for investigators to increase current understanding of the complex range of factors that affect the health and wellness of individuals and communities.

To date, wellness has been difficult to define scientifically because it encompasses all the delicate and exciting experiences that make life worth living. Physical vitality, mental alacrity, social satisfaction, a sense of accomplishment and personal fulfillment all contribute to wellness.

“Health seems like a no-brainer, but it is more than the absence of disease,” says John Ioannidis, MD, DSc, director of the Stanford Prevention Research Center (SPRC). The Wellness Living Laboratory (WELL) is the flagship effort of SPRC, and it aims to draw on the strengths and insights of world-renowned researchers at Stanford, using the best that rigorous science has to offer in approaching this important concept. “There’s clearly a lot of enthusiasm for obtaining actionable information about healthy living,” says Ioannidis.

The SPRC is particularly interested in diminishing health inequalities and serving disadvantaged populations, thereby contributing to Stanford University’s service to society.  SPRC is a unique gem within the vibrant Stanford community. For nearly half a century, SPRC has been making leading contributions to the field of disease prevention.

WELL aims to be the definitive platform to investigate, promote, and extend wellness for people across the socioeconomic spectrum. Studies in genetic science suggest that less than a quarter of health is dictated by immutable genetics, leaving over seventy-five percent influenced by other elements, such as lifestyle choices. Great scientific strides have been made in managing disease; yet, the real question is how do we prevent illness in the initial state.

WELL will engage tens of thousands of volunteers—called “citizen scientists”—in two initial locations: Santa Clara County, California, and Hangzhou, China, with plans to expand to other sites as additional funding is secured. The citizen scientists participating in this effort will contribute information to improve our understanding of what makes lives healthier.

Santa Clara County was selected because it is one of the most diverse counties in the United States and is home to people of many cultures and income levels. This diversity provides unique opportunities for investigators to increase current understanding of the complex range of factors that affect the health and wellness of individuals and communities.