Dr. Anju Vasudevan’s work on early embryogenesis of the forebrain vascular system has opened up an entirely new conceptual framework from which to view this important component of brain development. Her research focuses primarily on defining mechanisms governing central nervous system (CNS) angiogenesis, how it influences key events during brain development, and shapes our postnatal and adult behaviors. This work has implications for understanding and treatment of a variety of neuropsychiatric diseases like autism, epilepsy, schizophrenia, anxiety and depression.
Dr. Vasudevan received here PhD in Neuroscience from the University of Cologne, Germany, and completed her postdoctoral work at Massachusetts General Hospital/Harvard Medical School. From 2007-2020, Dr. Vasudevan was a faculty member in the Departments of Neurology and Psychiatry at Harvard Medical School. Dr. Vasudevan established the Angiogenesis and Brain Development Laboratory at McLean Hospital in 2011. In June 2020, Dr. Vasudevan joined HMRI as the Scientific Director of the Angiogenesis and Brain Development Research Program (www.hmri.org/neurovascular/), and Director of the Postdoctoral Program. Dr. Vasudevan is the recipient of the NARSAD Young and Independent Investigator Awards, and awards from the National Institute of Neurological Disorders and Stroke, and from the National Institute of Mental Health.
One in four people in the USA and worldwide suffers from some form of neuropsychiatric illness during their life. While drugs and therapies exist to treat some of the symptoms, there are no cures. Dr. Vasudevan’s research program investigates several key events of brain development and the ways those can go wrong, with the long-term goal of ensuring that early brain development remains on track. The lab uses a combination of developmental biology, genetics, cell biology, biochemistry, and imaging techniques in their research.
Endothelial cells are the building blocks of blood vessels. Work in Dr. Vasudevan’s laboratory has shown that blood vessel development molds brain cell development, and that there is remarkable endothelial cell diversity and function in the embryonic forebrain – a new insight. Blood vessel-related defects that originate during the brain’s earliest developmental stages play a role in neuropsychiatric illness in a way never before imagined. Intrinsic neuronal defects thus far believed to cause schizophrenia, epilepsy, autism and depression may in fact be a consequence of common molecular signals defective specifically in these endothelial cells. The lab is working to better understand how, why, and when this happens.
In addition, Dr. Vasudevan and her group are tapping into the potential of embryonic forebrain endothelial cells (mouse and human) in multiple ways to prevent the origin of diverse psychiatric symptoms by rescuing vascular defects in the prenatal brain, or by developing vascular therapies for repair and regeneration in the postnatal and adult brain.
Dr. Vasudevan’s contributions to science:
Dr. Vasudevan’s early works changed the dogma that endothelial cells are uniform, and that blood vessel formation is a passive process in response to neural signals. It depicted the diversity in embryonic forebrain vascular networks, by differentiating them as pial versus periventricular, based on anatomy, origin, growth patterns and developmental mechanisms. It changed notions of cerebral vascularization which implied that blood vessels sprout passively into the brain parenchyma from pial vascular plexuses to meet metabolic needs of growing neuronal populations.
Vasudevan A, Long JE, Crandall JE, Rubenstein JLR and Bhide PG. Compartment-specific transcription factors orchestrate angiogenesis gradients in the embryonic brain. Nature Neuroscience. 2008; 11(4): 429-39. PMID: 18344991
Vasudevan A and Bhide PG. Embryonic CNS angiogenesis: A new twist on an old tale; Cell Adhesion and Migration. 2008; 2(3), 167-169. PMID: 19262109
During 2011-2020, several works from Dr. Vasudevan’s laboratory documented new mechanisms by which periventricular endothelial cells instruct neurogenesis (the generation of neurons/brain cells), and neuronal migration (the movement of brain cells to the appropriate circuits) in the embryonic forebrain. It illustrated the intimate and symbiotic relationship between endothelial cells and neurons of the developing brain that respond meticulously and independently to common signals, depending on the cell type that secretes it. It showed that periventricular endothelial cells have intrinsic programs that can significantly mold neuronal development, and uncovered new insights into concepts and mechanisms of CNS angiogenesis from developmental and disease perspectives. It implicated periventricular endothelial cells as being contributory to a wide swath of neuropsychiatric diseases with – schizophrenia, epilepsy, autism, mood and depressive disorders topping the list, and shed light on an important new problem. Furthermore, it established direct links between abnormal blood vessel development and alterations in behavior, and brought fresh perspectives on the vascular origin of mental illness.
Won CK, Lin Z, Kumar PT, Li S, Ding L, ElKhal A, Szabo G and Vasudevan A. Autonomous vascular networks synchronize GABA neuron migration in the embryonic forebrain. Nature Communications. 2013; 4:2149 (1-14). PMID: 23857367
Li S, Haigh K, Haigh JJ and Vasudevan A. Endothelial VEGF sculpts cortical cytoarchitecture. The Journal of Neuroscience. 2013; 33(37):14809-15. PMID: 24027281
Li S, Kumar PT, Joshee S, Kirschstein T, Subburaju S, Khalili JS, Kloepper J, Du C, Elkhal A, Szabó G, Jain RK, Köhling R and Vasudevan A. Endothelial cell derived GABA signaling modulates neuronal migration and postnatal behavior. Cell Research-Nature. 2018; 28(2):221-248. PMID: 29086765
Choi YK and Vasudevan A., Mechanistic insights into autocrine and paracrine roles of endothelial GABA in the embryonic forebrain, Scientific Reports, 2019 Nov 7;9(1):16256. PMID: 31700116
Current work in the laboratory focuses on identifying new cellular and molecular substrates of neuropsychiatric disease origin and uses innovative approaches to harness the potential of CNS angiogenesis to find new cures. One project investigates whether pro-angiogenic compounds can be used to rescue neurovascular interactions during a critical developmental window and whether in doing so; it may be possible to ameliorate behavioral symptoms. In another project human endothelial cell transplantation is being tested for the possibility of rescue of neural circuits in the diseased brain. A third project seeks to identify new diagnostic tools and biomarkers to specifically distinguish between psychiatric disease categories through blood tests. Dr. Vasudevan envisions a future where the ‘healing touch’ of angiogenesis therapy will bring relief to patients suffering from mental health disorders.
Datta D, Subburaju S, Kaye S, Baruah J, Choi YK, Nian Y, Khalili JS, Chung S, Elkhal A, Vasudevan A. Human forebrain endothelial cell therapy for psychiatric disorders. Molecular Psychiatry, 2020 Jul 13. doi: 10.1038/s41380-020-0839-9. PMID: 32661257
Sivan S, Kaye S, Choi YK, Baruah J, Datta D, Ren J, Kumar AS, Fukumura D, Jain RK, Elkhal A and Vasudevan A. NAD+ mediated rescue of prenatal forebrain angiogenesis restores postnatal behavior. Science Advances, 2020; 6:eabb9766.