Nadia F. McMillan
B.A. Johns Hopkins University, 2009
8th Year MSTP
4th Year Medical Student
Advisor: Adan Aguirre, PhD
Department: Pharmacological Sciences, Stony Brook University
Graduate Program: Neuroscience
Title: Role of ADAM10 in the maintenance of adult neural stem cells
Abstract (undergraduate):
Neural stem cell (NSC) properties within the neurogenic niche of the subventricular zone (SVZ) of the postnatal mammalian brain are regulated by a diverse array of extrinsic and intrinsic signaling mechanisms. These neural stem cells exist in a tightly controlled environment where the niche composed of ECM proteins, adhesion molecules, and a network of vasculature instruct adult neural stem and progenitor cells (NSPCs) to remain in a quiescent, undifferentiated, or proliferating state. At the same time, NSPCs retain the flexibility to modulate both number and progeny in response to widespread physiological cues. ADAM10, a disintegrin and metalloproteinase, is thought to be responsible for the shedding of several cell surface proteins in the brain such as those involved in axon guidance and neuronal adhesion. Our data recently revealed an EGFR-dependent response of the SVZ niche to promote brain repair via Ncadherin signaling mediated by ADAM10 cleavage. These studies identified ADAM10 as a potentially important mediator of NSC properties within the SVZ niche. To further explore the role of ADAM10 in neural stem cells, we employ a transgenic mouse line in which ADAM10 is specifically deleted in NSPCs (Nestin-CRE/ADAM10fl/fl) of the adult SVZ. Our published data demonstrates that brain repair is disturbed when the ADAM10 pathway is abrogated in adult NSCs. Taken together, the data indicates ADAM10 mediated signaling pathways are not only essential for tissue homeostasis but also for repair. Preliminary data indicate that the signaling pathways affected by ADAM10 deletion regulate lineage progression, migration, and the maintenance of NSCs in their niche. The next challenge is to identify the signaling mechanisms involved in normal and pathologic conditions By studying the effects of these signaling mechanisms we hope to lay the groundwork for a feasible means of mobilizing endogenous neural stem cells for the therapeutic treatment of various central nervous system disorders (CNS) such as demyelinating disorders, alzheimers, or traumatic brain injury.
Awards:
CSCTR Travel Award
Publications:
(MSTP-supported publications indicated with an *)
Abernathy’s Surgical Secrets." Crisostomo PR, McMillan A, Meldum DR. Lung Transplantation(Chapter), pp 439-444. In "Surgical Secrets", Sixth Edition, Eds. Harken and Moore, Mosby, 2008.
*Michael Klingener, Manideep Chavali, Jagdeep Singh, Nadia McMillan, Alexandra Coomes, Peter J. Dempsey, Emily I. Chen, and Adan Aguirre1 (2010). N-Cadherin Promotes Recruitment and Migration of Neural Progenitor Cells from the SVZ Neural Stem Cell Niche into Demyelinated Lesions. J Neurosci. 34(29): 9590-9606
