Q&A: Chemical Biologist Ken Hsu to Use NSF CAREER Award to Fight Cancer

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Ken Hsu is working to understand and control the body’s inflammation response, with a focus on modifying immune cells to recognize and kill cancer.

A promising University of Virginia scientist, Ku-Lung (Ken) Hsu, an assistant professor of chemistry, has earned one of the National Science Foundation’s coveted Early Career Development Program Awards, which support junior faculty members who perform outstanding research and are regarded as exceptional teachers.

Part of the grant is used to integrate education and research in academic activities. Hsu’s award is for $681,000.

Hsu uses chemistry to control biological systems, particularly to modify the immune system to become an active combatant against cancer. His work – understanding and controlling the inflammation response – spans the search for new non-addictive drug options for treating pain, to modifying immune cells so they can recognize and kill cancer cells.

The five-year NSF CAREER grants are among the most prestigious available to young faculty in science and engineering, and are designed to provide significant resources to the early stage development of careers.

Many of Hsu’s laboratory studies are conducted in collaboration with clinical researchers in the School of Medicine’s Cancer Center as part of UVA’s efforts to enhance research into precision medicine – using immunotherapy to target life-threatening diseases at the fundamental molecular level.

Hsu discusses here his research and grant for readers of UVA Today.

Q. What drew you to this area of chemistry?

A. Chemical biology is an exciting area of chemistry because it is very creative, highly interdisciplinary and allows scientists to answer fundamental questions that ultimately improve human health through drug discovery and other new therapies. I enjoy the opportunity to work with experts in so many different fields, including pharmacology, pathology, neurology and cancer biology. As a result, I learn something new from each project.

My students also benefit greatly from being in this field because of an emphasis on collaborations, which increases diversity through individuals they interact with and expands the skillsets they obtain during their training. Medical research is becoming increasingly collaborative, so my students are becoming well-prepared for the research environments in which they will spend their careers.

“Activating the immune response to fight cancer represents a very exciting treatment modality and UVA is well-positioned to be a leader in this front. The UVA Cancer Center has been a major supporter of my research program, and I look forward to continued interactions and collaborations in this community.”

- Ken Hsu

Q. Describe the most compelling aspects of your latest research.

A. I am excited about two recent discoveries that embody research from our group in the field of chemical biology. Both reports are published in the journal Nature Chemical Biology.

In our first paper, we describe a new chemical reaction with broad applications for synthetic chemistry and drug discovery. The reaction we discovered possibly could come into common use for developing new treatments for cancer and other diseases in the future. This finding was especially rewarding because I teach related material in my organic chemistry course and our paper describes a new methodology for synthetic chemists and chemical biologists to “tune” chemical reactions for diverse real-world applications. This is compelling for my students, to know that what they are learning in class is also current and active to catalyze breakthrough research in our labs.

In our second report, our findings are directed toward fundamental discoveries in the realm of fat (lipid) molecules, which play a major role in the body’s metabolism at the cellular level. We used protein engineering to design artificial lipid kinase enzymes a specialized protein involved in cell growth, proliferation and other functions that can include the growth of cancers – in order to better understand how cells regulate their fat composition. To our surprise and delight, we narrowed in on a very specific region of these lipid kinases that allow us to control how they operate in cells. Our findings will teach us and others in the field a more effective way to design therapeutics to combat these enzymes when they misbehave.

Q. How will this grant allow you to connect your research with teaching?

A. The NSF CAREER Award will provide new opportunities for applying our chemistry and technologies to study how individual cells control the metabolism of fats and lipids. We plan to develop compounds that attach to enzymes to illuminate how cells are similar or distinct based on their metabolism – kind of like a molecular fingerprint. Our long-term goal is to create new opportunities for cell type discovery and push the boundaries of cell engineering.

The research is intimately connected to an educational outreach program designed to broadly impact Native American student communities by providing opportunities for UVA graduate students to teach how lipid biochemistry influences healthy food choices and eating behaviors in society.

Q. Where do you see your research going from here?

A. In the next five years, I am looking forward to applying our chemistry and technologies toward deeper understanding of lipid biology and metabolism in physiologically relevant models. We remain committed to discovery of new molecular pathways for immune system modulation, and our recent findings represent important steps toward our long-term goal.

Q. How promising is the future regarding immune system modulation?

A. Activating the immune response to fight cancer represents a very exciting treatment modality and UVA is well-positioned to be a leader in this front. The UVA Cancer Center has been a major supporter of my research program, and I look forward to continued interactions and collaborations in this community.

I believe the chemistry we are pursuing will provide new opportunities and technologies for exploring creative ways to study and control the immune system. Support from the NSF CAREER Award will pave the way for new ways to engineer immune cells for cancer and other potential disease indications.

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