Scholars

David Yan

Case Western Reserve University

Disease Areas

Immunology, Inflammation, Oncology, Rare/Orphan

Focus

Blocking XP01-Chromatin Binding Interactions Disrupts T Cell Activation in Autoimmune Diseases

Scholar Profile

2025 Harrington-MSTP Scholar

Autoimmune disorders affect 15 million Americans, challenging them with chronic pain, fatigue, flare-ups, and other physical symptoms, along with frustration and stress. Current treatment with immunosuppressive drugs can trigger side effects that make many patients feel worse, not better. Harrington Scholar and Case Western Reserve University (CWRU) Medical Scientist Training Program (MSTP) student, David Yan, hopes to restore normal living to these individuals by selectively blocking the transport protein, Exportin-1 (XPO1).

While Mr. Yan was an undergraduate among the researchers in CWRU’s Adams Laboratory, they discovered something unusual about XPO1. It was interacting with chromatin, the fibrous material that gives form to six feet of DNA strands and proteins neatly coiled inside the cell nucleus.

“This was not what XPO1 had been known to do for the past two or three decades of research,” Mr. Yan says. “Its roles in moving molecules, including proteins and RNA, from the cell nucleus into the cytoplasm were well understood but its involvement with T cell activation was not.”

As the lab began designing small molecules to target XPO1, Mr. Yan applied his problem-solving background in synthetic chemistry and biology.

“We designed small molecules that selectively inhibited XPO1’s chromatin interaction without affecting its nuclear transport function thus preserving normal cellular functions,” he explains. “Our small molecules are potent anti-inflammatories—good at turning off T cells without causing cell death—which could be helpful in T cell-driven diseases such as graft versus host disease (GVHD), pulmonary fibrosis, and rheumatoid arthritis, or even Type 1 diabetes.”

Leveraging insights from his Harrington advisors, Mr. Yan aims to refine a promising lead compound (B-001) for further testing while unraveling XPO1’s mysteries.

"Ultimately, the goal is to selectively turn off a portion of a patient's immune system when it's acting up and make people well again."