Gang Huang, Ph.D.

Huang lab focuses research on the crosstalk between the genetic and epigenetic regulators and signaling pathways that regulate hematopoietic stem cell self-renewal, differentiation, apoptosis, inflammation, and immune response as well as mechanisms underlying ineffective hematopoiesis. In a paper published in Cancer Discovery in 2018 (PMID: 30139811), Dr. Huang was the first to identify the downregulation of mitochondria complex II (also known as succinate dehydrogenase, SDH) subunits and assembly factors (SDH genes) along with some other Krebs/TCA cycle enzymes in a subset of MDS patients. Simultaneously, he characterized genetically distinct mouse models of MDS and identified the downregulation of subunits and assembly factors of SDH in the hematopoietic stem and progenitor cells (HSPCs) in the established MDS mouse models, independent of the inducing genetic/epigenetic alterations. These works in mice paved the way for clinical research focusing on SDH genes and eventually development of novel drugs and therapeutic strategies, benefiting many patients with MDS around the world. MDS primarily occur in the aging population or secondarily occur following therapy for unrelated cancers (therapy related MDS, tMDS). Allogeneic stem cell transplantation is the only curative treatment, but has marked limitations in the majority of MDS patients. The current standard-of-care focuses on HMAs, which invariably results in resistance and disease progression. There is a dire need for new therapeutics; however, the field lacks a clear understanding of the molecular pathobiology underlying MDS, which is requisite to develop adequate therapies. To fill the gaps in potential MDS treatments, Dr. Huang will develop a new research program focusing on defining the role of low SDH in MDS-genesis, mitochondrial metabolism and a-KG–dependent dioxygenases (2OGDDs) inhibition, and determining upstream regulation of SDH by MDS-related mutations and SDH induction by HMAs.

Huang lab focuses on a wide scope of myeloid malignancies including MDS, MPN and acute leukemia. In addition, his findings on the mechanistic roles of crosstalk between mitochondrial activity and genome/epigenomes in MDS pathogenesis not only impact on the field of MDS research, but also on a variety of tumors including MPN, leukemia, lymphoma, renal cell carcinoma, gastrointestinal stromal tumor (GIST), glioma,  and other solid tumors, as dysregulation of balanced mitochondrial metabolism is broadly involved. Dr. Huang has published over 100 papers, many in high-impact journals, including EMBO J., Blood, Mol. Cell Biol., Nature Genetics, Nature, Nature Communications, Mol. Cell, Cancer Discovery, Haematologica, and Leukemia.