Kosaka Best Basic Science Research Award Winner: Shufang He, PhD

Shufang He, PhD, from Stanford University and The Second Hospital of Anhui Medical University, was recognized with the Kosaka Best Basic Science Research Award for her research on “Leveraging TRPV1 genetic divergence between avian and mammalian species to develop a TRPV1 knock-in mouse and a novel analgesic” during the Kosaka Best Abstract Award Session on May 16 at the IARS 2021 Annual Meeting. She discusses how a quandary about why birds can eat hot peppers and mammals avoid them led her to this particular research topic as well as the implications of her research.

What is your professional title and institution? How long have you been there?

From December 2017 to June 2020, I was a visiting instructor in the laboratory of Dr. Eric Gross in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University. I am presently Associate Professor in the Department of Anesthesiology and Perioperative Medicine at The Second Hospital of Anhui Medical University.

Do you conduct your research by yourself or with a team?

This study was conducted under the guidance of Dr. Eric Gross and would not have been possible without assistance from researchers Vanessa Zambelli, Pritam Sinharoy, Yang Bian, Freeborn Rwere, and Ye Zhang. The international representation for this abstract has been amazing with investigators from Brazil, Zimbabwe, China, India, and the United States, all working together in the Gross Lab.

Is there anyone else you wish to acknowledge as part of this research team?

I want to thank Dr. Hong Zeng and Dr. Zhuanfen Cheng from the Transgenic, Knockout and Tumor model Center (TKTC) at Stanford University for assistance in generating the knock-in mice.

What drew you to this area of research?

My past research focused on opioid-induced cardio-protection against perioperative myocardial ischemic injury and the interaction with the capsaicin receptor TRPV1 (transient receptor potential vanilloid 1). In 2017, after arriving at Dr. Gross’s lab, we started talking about the way birds eat hot peppers, which have the ingredient capsaicin, while most mammals naturally avoid hot peppers. It’s very interesting! In addition, birds have a functional TRPV1 receptor. However, due to the genetic divergence in TRPV1, birds are less sensitive to capsaicin, so they are able to eat the hot peppers that mammals avoid. This prompted us to ask, can we manipulate the TRPV1 receptor to reduce responses to noxious stimuli in mammals? This is also an important question to address due to the opioid crisis.

What is the goal of your research?

The TRPV1 receptor, which is crucial in relaying nociceptive signals to the brain, is an attractive target to regulate pain transduction. Interestingly, the TRPV1 receptor in avian species is naturally resistant to noxious stimuli, a genetic advantage for birds that allows them to eat the spicy peppers. By gene-editing the rodent TRPV1 receptor to carry a single TRPV1 amino acid, one that is genetically divergent between mammals and birds, we thought we could manipulate the mammalian TRPV1 receptor to mitigate, but not eliminate, TRPV1-mediated responses to pain. The goal, then, was to see if we could mimic the effect of gene editing TRPV1 by targeting this region of the TRPV1 receptor with a cell permeable peptide, potentially a lead compound for a novel analgesic.

What’s the most significant finding?

By gene editing the rodent TRPV1 receptor to carry a single TRPV1 amino acid that is genetically divergent between birds and mammals, we reduced the biochemical and behavioral responses to noxious insults in rodents. Further, designing a cell permeable peptide to target this region mimicked the rodent effect. We found a promising lead compound that can be refined and used in developing a novel analgesic.

Will your findings directly affect patient care?

Right now, our findings do not directly affect patient care, but they may lead to the development of an analgesic that does not target the opioid receptor.

How do you feel about receiving the Kosaka Best of Meeting Award? How will it affect your career?

I am really excited and honored to receive the Kosaka Award. It will definitely have a positive effect on my research trajectory and bolster the confidence I have in my research direction. In addition, I’m glad that other investigators will see my research at the IARS meeting and the Kosaka Awards session. I look forward to sharing my work with others and fostering future collaborations.

How has the COVID-19 pandemic affected your research and work over the past year?

The COVID-19 pandemic affected me a lot. I was working on the TRPV1 project as a visiting instructor at Stanford University and the program was to end in May 2020. Unfortunately, in March of 2020 the lab closed, all experiments were interrupted, and we were asked to stay at home. I had difficulty finding a flight back to China while my Visa was expiring — this was a tough time! However, I’m optimistic about my future research directions and, hopefully, the worst part of the pandemic is over.

How has COVID-19 changed your learning/education needs? Do you see any changes becoming permanent?

During the COVID-19 pandemic, most courses and meetings moved online. This has turned out to be an unexpected benefit and we are now better at communicating with people via Zoom and other media.

There are some permanent changes. For example, the new normal is temperature checks or thermal imaging cameras at the entrances of airports and railway stations. Many people may want to continue working and studying from home.