photo of Chongmin Huan, MD, PhD

Chongmin Huan, MD, PhD

Assistant Professor

Research Description

Our team of researchers, which includes Ms. Sailee Chavan (PhD student), Ms. Shreya Desikan (MD/PhD student), Dr. Christopher Roman (Cell Biology), Dr. Ellen Ginzler (Medicine: Rheumatology) and myself, has a keen interest in the causes of autoimmune diseases and developing more effective treatments for them. We are using genetically modified mouse models and human samples to study the self-protective mechanisms of B cell tolerance that guard against systemic lupus erythematosus (lupus), an autoantibody-mediated disease that remains a serious clinical challenge.

We focus on the immune tolerance role of sphingomyelin synthase 2 (SMS2), an enzyme that produces sphingomyelin and diacylglycerol on the plasma membrane. We have reported that SMS2 prevents lupus pathogenesis in mice by activating a B cell tolerance mechanism in the germinal center, where random somatic hypermutation of immunoglobulin genes naturally generates lupus autoreactive B cells at a low frequency. In the normal germinal center, we showed that SMS2 is highly upregulated specifically in these lupus autoreactive B cells, where it triggers cell death via activating the pro-apoptotic function of protein kinase C delta (PKCd) by providing diacylglycerol (see figure and our publication). Evidence that this is a critical tolerance mechanism that protects against lupus includes: SMS2 or PKCd deficient mice exhibit a lupus-like phenotype; lupus patients’ B cells have substantially reduced SMS2; and mutations in PRKCD, the gene encoding PKCd, cause lupus autoimmunity in humans. Notably, pharmacologic activation of SMS2 attenuates lupus pathogenesis in NZBWF1 mice, the gold standard preclinical murine lupus model. Therefore, the SMS2/PKCd tolerance pathway appears to be essential and targetable for protecting against lupus pathogenesis in mice.

Currently, we are studying how SMS2/PKCd tolerance pathway becomes impaired in patients with lupus and the role of this tolerance pathway in the mechanisms of action of existing medications used to treat lupus. We believe that these studies may lead to breakthroughs in our understanding of the underlying drivers of autoimmune disease and help develop new and more effective treatments.


figure of cell

Figure: An illustration of the pro-apoptotic SMS2/PKCd pathway in a lupus anti-dsDNA GC B cell (adapted from Ou et al, Cell Reports 2021 Aug 31;36(9):109624. Article Link).


Complete List of Published Work in MyBibliography

College of Medicine: 

  • Histology
  • Physiology:
    • Small intestine & Pancreas
    • Carbohydrate, Water and Electrolyte Absorption

School of Graduate Studies, Program in Molecular and Cellular Biology: 

  • Principal Investigator/Graduate Student Supervisor

Department Links

Cell Biology