P.O., Box 208082
New Haven, CT 06520-8082
Besides IA, another major focus of my lab has been the study of molecular genetics and biology of cerebral cavernous malformations (CCM) in collaboration with Angeliki Louvi, PhD.
CCM is a major form of hemorrhagic stroke, affecting nearly 0.5% of the population. CCMs are abnormally dilated vascular channels in the brain that can lead to bleeding or seizures (Fig. 2). Our work over the past 15 years on this disease have lead to several seminal contributions, resulting in over 20 publications in peer-reviewed journals and over 40 national and international presentations. Our findings range from localization of the first gene that causes CCM to 7q (PNAS 1995 92(14):6620-4) to the demonstration of a single disease-causing mutation in Hispanic-Americans (N Engl J Med. 1996 ;334(15):946-51) to large scalemutational analysis of CCM genes (J Neurosurg 2003; 99(1):38-43) to molecular biological work molecules aimed at understanding their biological function (Fig. 3) (PNAS 2002; 99(16):10677-82 , Neurosurg 2004; 54(4):943-9, Stroke 2006; 37(2):518-23, Neurosurg 62(4):930-8, 2008 , Stroke 2008 in press). This body of work spanning the past 15 years, is representative of our general philosophy of identification of disease genes followed by the dissection of disease biology. This work now places us in a unique position, for the first time, to attempt to develop novel therapies for CCM.
This work is currently funded by a R01 from NINDS/NIH.