DNA Sequencing

Using DNA Sequencing to Better Fight Cancer and Infections

Dr. William Kerr loves to solve problems and says, "Cancer is one of the largest health problems we face as a society." He is extremely motivated to take on "the intellectual challenge of tricking the immune system without causing autoimmunity." Over the years researchers have made tremendous advances in cancer research, but Dr. Kerr believes we still need to keep forging ahead to develop more effective therapies to treat all forms of cancer. Dr. Kerr stays motivated by solving problems one step at a time, and right now, his research is focused on killing cells that do not belong in the body. 

Dr. Kerr says, "The catalyst for me was going into science realizing the medical profession was not for me.” Dr. Kerr became excited by research and trying to understand fundamental processes in the body at a molecular level. This led him to a stint as a group leader at a biotech company in the San Francisco Bay Area. He currently works at Upstate Medical University and he says the facilities there “are a significant component of his research."

Dr. Kerr earned his PhD in Molecular & Cellular Biology at the University of Alabama at Birmingham in 1987. By 1993, Kerr finished his post-doctoral fellowship at Stanford University working with the late Leonard Herzenberg, a geneticist and National Academy member, where he developed a method to "trap or find genes that turn when immune cells are activated." Dr. Kerr says, "At that time there was no genome sequence and genes involved in immunity had yet to be defined. This new technology allowed me to identify two genes, SHIP1 and LRBA, which play a key role in the immune system. I am still studying them over 25 years later." DNA sequencing is the process of determining the precise order of nucleotides, or bases within a DNA molecule. Ultimately the purpose of identifying genes and their structure is to help immunologists, like Dr. Kerr, better understand what makes immune cells tick, and therefore, better understand how we might improve their ability to fight cancer and infections.

Dr. Kerr has focused much of his research over the last 20 years on trying to understand what one gene called SHIP1 does in the body. To do this, he created mice that are unable to turn on or use their SHIP1 gene which he refers to as SHIP1 deficiency. Since arriving at Upstate Medical, Dr. Kerr’s group has identified chemicals that turn off the SHIP1 gene (SHIP1 inhibitors). In collaboration with John Chisholm, a chemist at Syracuse University, Dr. Kerr and the group found this has a variety of dramatic effects on immune function. So far, Dr. Kerr’s research has been successful in laboratory mice. He has successfully used SHIP inhibitors to reverse obesity in mice fed a high-fat diet. Intriguingly, a different version of one SHIP1 inhibitor can also jump start the immune system into fighting cancer in mice, including both lymphoma and colon cancer. Dr. Kerr states, "Due to our work, immunologists, and hopefully one day oncologists, will have a tool in their toolkit to turn on immune cells so they can better detect the presence of cancer cells and then them. This approach may also work for HIV-infected cells infected by viruses, like HIV, or bacteria like tuberculosis."

There are many challenges that come with solving such complex problems. Dr. Kerr says, "You look for those ah-ha moments that provide an insight into how you might approach developing a cure." For Dr. Kerr, one of those key motivating factors came when a graduate student made an observation that led to new discoveries. When his team was studying a certain kind of SHIP1 deficient mice, one student noticed that older mice with the defective SHIP1 gene did not gain as much weight as their wild-type or normal counterparts. This led them to test if SHIP inhibitors could chemically inactivate SHIP1 and reduce weight in obese mice. They did! This work was published in Journal of Clinical Investigation Insight and sparked a new challenge for Dr. Kerr. He says, "When I started this research in the late 1980s, I began understanding things on a fundamental level. Having done that to a significant degree, I would now like to take what we've learned and apply that to human diseases such as obesity, cancer, and perhaps even Alzheimer’s which new research suggests might be controlled by immune cells in the brain called microglia."

A lot of Dr. Kerr's breakthrough research has come from laboratory mice. The next step is to work with Cornell Veterinary School of Medicine to test these treatments on dogs and cats as a prelude, if successful, to eventual testing in humans. Dr. Kerr wonders, "Can we take this research to the clinic and make a difference in people’s lives while developing a commercially successful company that benefits the State of New York economically? A possible win-win for New York and SUNY."

Dr. Kerr also hopes one day to use SHIP1 inhibitors to boost immunity in the patient’s cancers and give them a better chance for a successful recovery. These type of immunotherapies have been a “big breakthrough for cancers like melanoma, lung cancer, and lymphoma.” Dr. Kerr’s research on a new immunotherapy using a SHIP1 inhibitor to treat lymphoma and colon cancer was recently published in the prestigious journal, Science Signaling. SHIP1 inhibitors may also offer a new way, and potentially less toxic way, of boosting immunity to cancer. Current immunotherapies that can be very effective but come with significant side effects that are, in some cases, life-threatening.

With Dr. Kerr’s proven research in mouse models, he hopes that further exploration of the relationship between SHIP1 studies and the immune system in cancer and obesity will be a major focus of his lab at Upstate Medical University in the coming years. He is also moving his research closer to the clinic as he recently co-founded a biotech firm, Alterna Therapeutics, along with Chris Meldrum of Golden Pine Ventures. Dr. Kerr and Alterna Therapeutics also received a seed grant from the SUNY Research Foundation. He hopes Alterna Therapeutics will eventually become a commercial success and that these types of biotech ventures founded by SUNY faculty will attract other researchers and pay dividends for New Yorkers. He says, "I truly appreciate the Empire Scholar Program, it is one of the reasons I came to SUNY Upstate Medical University. I’m truly grateful the State of New York is a key supporter of transformative biomedical research through this and other state-wide initiatives."

While National Institute of Health funding has seen bipartisan support in Congress, Dr. Kerr hopes federal funding can make greater strides to keep pace with inflation. However, the competition is quite intense for National Institutes of Health grants and thus, “in order to be successful in research funding, you have to also seek support from foundations, initiatives, and be creative with state, local, and private sector opportunities. The Paige Arnold Butterfly Run is a local charity that has made much of our recent success in the lab happen due to their generous support.”

He says, "I’m pretty satisfied with where we are right now. There is a lot of hard work still to be done to translate our recent findings to the clinic or bedside, but nonetheless, my scientific journey has been very rewarding and fulfilling. Another example of how you should follow your heart, have confidence in your abilities and not be too afraid to take some risks. These don’t always pay off, but sometimes they do, and maybe in a way that improves people's lives."

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