Dmitriy Atochin, M.D., Ph.D.
Cardiovascular Research Center, Research Institute
Assistant Professor of Medicine
Harvard Medical School
Cardiology, Massachusetts General Hospital
|PhD Institute of Evolutionary Physiology & Biochemistry 1992|
|MD Institute of Medicine 1983|
I received my MD in Siberian State Medical University (Tomsk) and PhD in Institute of Evolutionary Physiology and Biochemistry (St.Petersburg) in Russia. I was postdoctoral fellow in Institute of Environmental Medicine of University of Pennsylvania (laboratories of Drs. D. Buerk, S. Thom and V. Muzykantov) and in CVRC of MGH (laboratory of Dr. P. Huang), where I was promoted to Instructor and Assistant Professor.
My research combines mouse genetics, detailed physiologic and hemodynamic measurements, and animal models of human disease, including stroke, atherosclerosis, and diabetes.
My current work focuses on the role of Akt-eNOS-cGMP axis in cerebrovascular dysfunction. My publications demonstrated that mice that carry specific S1177D mutation in eNOS gene are protected against stroke (Journal of Clinical Investigation, 2007), and that they show less obesity and metabolic abnormalities on high fat diet (Biochemical and Biophysical Research Communications, 2013).
We show that unphosphorylatable eNOS impairs vascular reactivity to nitric oxide and is associated with incomplete reperfusion, larger infarct size, and worse metabolic profile, suggesting that S1177 eNOS is protective in ischemic stroke. We have found that increased phosphorylation of eNOS on serine 1177 normalized vascular abnormalities in type 2 diabetic mice and protect them against reperfusion injury (Stroke, 2013).
I demonstrated that sGC alpha 1 deficiency impairs vascular reactivity to nitric oxide and is associated with incomplete reperfusion, larger infarct size, and worse neurological damage, indicating that cGMP generated by sGC alpha1 is protective in ischemic stroke (Stroke 2010).
The hydrogen clearance method of absolute cerebral blood flow measurement which I use provides absolute measurements as opposed to relative measurements seen with laser Doppler or other commonly used approaches. It has become more accepted, as comparison of genetically altered mice with control animals requires consideration of baseline physiologic differences. I used the hydrogen clearance technique to assess the state-of-the-art novel method of Doppler optical coherence tomography in cerebrovascular physiology (Journal of Cerebral Blood Flow and Metabolism 2011).
We demonstrated that C-reactive protein, a widely accepted marker of cardiovascular diseases, causes insulin resistance through Fcγ receptor IIB-mediated inhibition of skeletal muscle glucose delivery (Diabetes 2012). I showed that C-reactive protein increases the severity of stroke outcome (International Stroke Conference 2012). This demonstrates that C-reactive protein is not just a marker, but also plays a mechanistic role in cerebrovascular and cardiometabolic diseases, opening the possibility for additional treatment and prevention strategies.
The overall unifying theme behind my work is to apply in vivo physiology and disease models and in vitro vascular reactivity measurements, to genetic models relevant to the NO pathway, such as nNOS, eNOS, iNOS, soluble guanylate cyclase, and C-reactive protein. My work is important because it can lead to the development of new approaches to treat cardiovascular and cerebrovascular disease in the setting of diabetes and metabolic abnormalities.