Weikang Cai received his B.S. degree from Nanjing University in China and his Ph.D. degree in Biochemistry with Dr. Douglas A. Andres at the University of Kentucky. He obtained his postdoctoral training under the mentorship of Dr. C. Ronald Kahn at Joslin Diabetes Center, Harvard Medical School. He is a current recipient of the Research Scientist Development Award (K01) from the National Institute of Diabetes and Digestive and Kidney Diseases.
During his training, Cai developed a passion and research interest in astrocytes, the most abundant glial cells in the brain. Astrocytes play many fundamentally important roles in normal brain function, including brain metabolism, synaptic homeostasis, blood-brain barrier integrity, and injury repair. Upon microenvironmental changes, astrocytes can actively modulate the synaptic plasticity and neuronal activity, by releasing "gliotransmitters" such as glutamate, D-serine, and ATP. The dysfunction of astrocytes and astrocyte-neuron communication may contribute to the progression of many neurological diseases. Supporting this hypothesis, abnormal astrocyte density and function are evident in many types of neurological diseases, including Alzheimer's disease, major depression, stroke, and diabetes.
Cai's group has recently identified a previously unrecognized brain insulin action, in which insulin regulates exocytosis of ATP by astrocytes. This astrocyte-initiated signaling contributes to the modulation of the dopaminergic neural circuit and depressive-like behavior in mice. This finding provides a potentially important molecular link for the comorbidity of diabetes/insulin resistance and depression and may have more general implications on other neurological conditions.
Moving forward, the main research interest of Cai's laboratory is to understand the molecular mechanisms by which astrocytes respond to external signals to modulate brain metabolism, neuronal activity, and behavior. Further, Cai Lab aims to investigate the contribution of these astrocyte-initiated pathways on the progression of neurological complications related to diabetes, including depression, neurodegenerative diseases, and painful neuropathy. Cai Lab uses both in vitro (primary cell cultures) and in vivo (transgenic mice) models to understand the crosstalk between astrocytes and neurons in health and diseases. Trainees in the lab are expected to lead an independent research project within the scope of our research interest. They will receive extensive training ranging from basic biochemistry, and molecular biology, to integrated physiology and neurobiology.
Recent Projects and Research
- Insulin signaling and diabetes on astrocyte "gliotransmission", dopamine system and depression
- Astrocytes, somatosensory neural circuit and painful diabetic neuropathy
- Role of astrocytes in the development and progression of Alzheimer's disease
- Ramirez AK, Dankel SN, Rastegarpanah B, Cai W, Xue R, Crovella M, Tseng YH, Kahn CR, Kasif S. Single-cell transcriptional networks in differentiating preadipocytes suggest drivers associated with tissue heterogeneity. Nat Commun. 2020 Apr 30;11(1):2117. PMID: 32355218.
- Soto M, Cai W, Konishi M, Kahn CR. Insulin signaling in the hippocampus and amygdala regulates metabolism and neurobehavior. Proc Natl Acad Sci USA. 2019 Mar 26;116(13):6379-6384. PubMed PMID: 30765523. *These authors contribute equally.
- Sakaguchi M, Cai W, Wang CH, Cederquist CT, Damasio M, Homan EP, Batista T, Ramirez AK, Gupta MK, Steger M, Wewer Albrechtsen NJ, Singh SK, Araki E, Mann M, Enerbäck S, Kahn CR. FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism. Nat Commun. 2019 Apr 5;10(1):1582. PubMed PMID: 30952843.
- Wang G, Meyer JG, Cai W, Softic S, Li ME, Verdin E, Newgard C, Schilling B, Kahn CR. Regulation of UCP1 and Mitochondrial Metabolism in Brown Adipose Tissue by Reversible Succinylation. Mol Cell. 2019 May 16;74(4):844-857.e7. doi: 10.1016/j.molcel.2019.03.021. Epub 2019 Apr 15. PubMed PMID: 31000437.
- Batista TM, Garcia-Martin R, Cai W, Konishi M, O'Neill BT, Sakaguchi M, Kim JH, Jung DY, Kim JK, Kahn CR. Multi-dimensional Transcriptional Remodeling by Physiological Insulin In Vivo. Cell Rep. 2019 Mar 19;26(12):3429-3443.e3. PubMed PMID: 30893613.
- Cai W, Xue C, Sakaguchi M, Konishi M, Shirazian A, Ferris HA, Li ME, Yu R, Kleinridders A, Pothos EN, Kahn CR. Insulin regulates astrocyte gliotransmission and modulates behavior. J Clin Invest. 2018 Jul 2;128(7):2914-2926. PubMed PMID: 29664737.
- Altindis E, Cai W, Sakaguchi M, Zhang F, GuoXiao W, Liu F, De Meyts P, Gelfanov V, Pan H, DiMarchi R, Kahn CR. Viral insulin-like peptides activate human insulin and IGF-1 receptor signaling: A paradigm shift for host-microbe interactions. Proc Natl Acad Sci USA. 2018 Mar 6;115(10):2461-2466. PubMed PMID: 29467286.
- Cai, Sakaguchi M, Kleinridders A, Gonzalez-Del Pino G, Dreyfuss JM, O'Neill BT, Ramirez AK, Pan H, Winnay JN, Boucher J, Eck MJ, Kahn CR. Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression. Nat Commun. 2017 Mar 27;8:14892. PubMed PMID: 28345670. *These authors contribute equally.
- García-Cáceres C, Quarta C, Varela L, Gao Y, Gruber T, Legutko B, Jastroch M, Johansson P, Ninkovic J, Yi CX, Le Thuc O, Szigeti-Buck K, Cai W, Meyer CW, Pfluger PT, Fernandez AM, Luquet S, Woods SC, Torres-Alemán I, Kahn CR, Götz M, Horvath TL, Tschöp MH. Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell. 2016. Aug 11;166(4):867-80. PMID: 27518562.
- Kleinridders A, Cai W, Cappellucci L, Ghazarian A, Collins WR, Vienberg SG, Pothos EN, Kahn CR. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proc Natl Acad Sci USA. 2015 Mar 17;112(11):3463-8. PubMed PMID: 25733901.
Honors and Awards
- 2007: Academic Excellence Award
- 2007: Research Challenge Trust Fund I Fellowship
- 2008: Kentucky Opportunity Fellowship
- 2009: Max Steckler Award
- 2010: Thomas C. Vanaman Award for Presentation in Biochemistry
- 2019: NIDDK Mentored Research Scientist Development (K01) Award
Courses Taught at New York Tech