Chi Zhang

Postsurgical pain causes significant suffering. Continuous reliance on opioid analgesics can lead to severe side effects and accidental death. Therefore, there is an urgent need to develop nonopioid therapies for managing postsurgical pain. We demonstrated that local application of a naturally occurring biologic derived from human birth tissues (amniotic membrane, AM) attenuated established postsurgical hypersensitivity without exhibiting known side effects of opioid use in mice. Importantly, preemptive treatment also prevented postsurgical pain from transitioning to a prolonged state. This effect was achieved through diverse modes of actions, including direct inhibition of nociceptive dorsal root ganglion neurons via CD44-dependent pathways and indirect pain relief by attenuating immune cell recruitment. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility. HC-HA/PTX3 replicated neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of a naturally derived biologic from human birth tissues as an effective nonopioid treatment for postsurgical pain, and unravel the underlying mechanisms. This study was done in Yun Guan’s lab in the Department of Anesthesiology and Critical Care Medicine.

Questions & Answers

Why did you choose Johns Hopkins for your work?

I chose Johns Hopkins for its reputation in high academic standards, world-class research environment and innovative research opportunities.

What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?

I am deeply grateful to receive the A. McGehee Harvey Award — it is a major milestone in my career development. Personally, it validates my dedication and boosts my confidence to continue pursuing my career goals. Professionally, receiving this award makes my research more visible and will open up new opportunities for potential collaboration, funding and career advancement.

Dr. A. McGehee Harvey was known for his pioneering work in applying research to medical care. Receiving an award in his name is particularly suitable for our work in Dr. Yun Guan’s lab, where we strive to identify new targets and optimize strategies for treating pathological pain conditions. I am proud that the translational value of our work was recognized by the YIDP committee, resulting in the A. McGehee Harvey Award.

What contributed to your project’s success?

First, I attribute the project’s success to the support from my PI, my colleagues, and the Department of Anesthesiology and Critical Care Medicine (ACCM). Dr. Yun Guan, my PI, always motivates me to think openly and encourages me to try out new ideas. Moreover, he mentors such an incredible team, from whom I receive continuous help and learn a lot, which helped me prepare my techniques well before leading this project. I also benefit a lot from the excellent research environment created by the ACCM department. Every year, the department hosts a Research Day event, where researchers communicate research ideas and findings with each other. Second, the support from my family allows me to focus on my work and advance my career. Most importantly, I have been greatly inspired by my husband, who also did his postdoctoral training at Hopkins and recently started his own lab. His determination and perseverance in the face of challenges always motivate me.

What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins?

Young Investigators’ Day provides us with a platform to showcase our work, receive feedback from peers and experts, and build connections within the research community. This event exemplifies the exceptional academic environment at Johns Hopkins, which fosters the growth of the next generation of researchers.

What has been your best/most memorable experience while at Johns Hopkins?

I have had the privilege of getting to know many talented individuals who have brought new perspectives and insights, refreshing my understanding of science and the world.

What are your plans over the next year or so? Graduating, looking for faculty positions, etc.?

I will start a junior faculty position and apply for funding opportunities to support my independent research.

Tell me something interesting about yourself that makes you unique. Do you have any special hobbies, interests or life experiences?

I have a deep passion for singing, finding strength in its melodies — a hobby I intend to cherish for life. A few years ago, to celebrate the accomplishment of my Ph.D. training, I recorded an album featuring my favorite songs.