Dr. Naiche Adler is the Scientific Director of the Kitajewski lab, in which she which contributes extensive mentorship of graduate and undergraduate students, grant writing, experimental design and prioritization, and lab administration.

Dr. Adler is a developmental and vascular biologist with a lifelong interest in using model systems to study developmental processes with applications to human health.  She has studied the development of a number of organ systems, giving her a broad range of experience in physical and genetic manipulations of the mouse. In particular, she has comprehensive expertise with complex mouse genetics, including creation, validation, and use of tissue- and temporal-specific mutations, reporter lines, and combinations of gain-of- and loss-of-function mutations to isolate genetic pathways.  Her current work is focused on two major themes: context-specific endothelial Notch signaling, and the importance of endothelium in breast cancer growth and metastasis.

Notch signaling: Notch signaling is a powerful regulator of vessel formation and endothelial cell behaviors. While Notch signaling is generally considered to play an anti-angiogenic role, this effect has largely been ascribed to Notch1, the most well studied of the Notch genes. The Kitajewski lab’s recent work has shown that other members of the Notch pathway are highly context-specific and may have pro-angiogenic effects. We have shown that the Notch ligand Jag1 in the post-ovulation follicle inhibition can either block angiogenic sprouting or dramatically increase vessel diameter, depending on degree of ovarian stimulation.  We have recently begun to identify targets of endothelial Notch signaling that mediate different aspects of the Notch phenotype. A novel endothelial Notch target, Rnd1, specifically mediates the anti-migratory effects of Notch signaling without changing other Notch endothelial phenotypes, while another novel target, Unc5B, specifically modulates endothelial proliferation and polarization in response to blood flow. Ongoing work in the lab is elucidating the distinct and overlapping roles of two Notch proteins, Notch1 and Notch4.

Endothelial roles in breast cancer: interactions between tumor cells, immune cells, and endothelial cells are critical for the dissemination and engraftment of metastases. We have recently shown that an anti-Notch4 antibody alters tumor vasculature and significantly reduces tumor growth in several mouse tumor models, including breast cancer. Current work in the lab is focusing on the roles of Notch signaling in tumor-associated lymphatics, particularly in facilitating lymphovascular invasion. We are also examining the role of endothelial Ackr1 in interactions between endothelium, immune cells, and metastatic breast cancer.