In this section
Developmental vascular biology
Understanding how blood vessels form — and what happens when that process goes awry — could lead us to better tools to help kids with vascular conditions such as hemangiomas and solid tumors.
What is developmental vascular biology research?
The developmental vascular biology program, led by Ramani Ramchandran, PhD, investigates the basic mechanisms of blood vessel formation in vertebrates and how those vessels contribute to diseases. Our researchers study developing zebrafish and mouse embryos to gain insights into vascular conditions associated with children, such as hemangiomas and solid tumors.
We study cells called angioblasts, which eventually differentiate into arteries or veins. The basic mechanisms of this process often are deregulated in disease, so better understanding vessel formation is critical to generating new treatments for conditions affected by deregulated vessel growth.
During development, blood vessels adapt to the specific needs of the organ they supply. For example, in the lungs, the vasculature becomes highly specialized to provide efficient gas-exchange by participating with alveoli. Development of lung alveoli requires complex interactions among blood vessels, other specialized cells and the extracellular matrix. Defects in any one of these elements will adversely affect alveolar development and can lead to conditions such as emphysema and infant bronchopulmonary dysplasia.
In addition to studying blood vessel formation, our researchers are also developing tools for performing drug screens using zebrafish embryos, which will identify targets and potential drug leads for treating pediatric vascular conditions.
Ramani Ramchandran, PhD, professor of pediatrics
Vice chair for Research, Department of Obstetrics and Gynecology (MCW)
Patrick J. and Margaret G. McMahon Professor in Obstetrics and Gynecology (MCW)
The Developmental Vascular Biology Program, under the directorship of Dr. Ramchandran, is home to graduate students, post-doctoral fellows, undergraduate students and faculty. Dr. Ramchandran began his research career at the Georgia Health Sciences University (formerly called Medical College of Georgia) in Dr. Dorothy Tuan's laboratory in 1992 where he studied the transcriptional mechanisms controlling hematopoiesis. He then joined Dr. Vikas Sukhatme's laboratory in 1997 as a post-doctoral fellow at Beth Israel Deaconess Medical Center, Harvard Medical School. In Dr. Sukhatme's laboratory he studied the role of basement membrane proteins in endothelial cell growth and the implications of this process for tumor growth. His work at Harvard primarily focused on understanding the mechanisms of angiogenesis, the growth of new blood vessels from pre-existing vessels, and how this process affects tumor growth. In 2002, he was recruited to the NIH on receipt of the National Cancer Institute Scholar Award, and established his first independent research program studying the developmental mechanisms of vascular biology. In 2007, he was recruited to the Children's Research Institute at the Medical College of Wisconsin where he currently serves on the faculty as a professor in the Department of Pediatrics. At CRI, Dr. Ramchandran made a serendipitous discovery that led to the identification of mutations in two genes sucrose non-fermenting related kinase-1 (snrk-1) and dual specific phosphatase-5 (dusp-5) in patients with vascular anomalies. Since then his research has focused on the role of these genes in both normal and abnormal vascular development process in disease. He has also established a robust drug discovery program that is geared towards identifying small molecules targeting critical gene products responsible for diseases affected by deregulated vascular growth.
I support the Developmental Vascular Biology Program in terms of its day-to-day academic activities, and manage most of the logistics associated with these activities for Dr. Ramchandran, post doctoral fellows and technicians in his lab. Some of my administrative duties include coordinating grant submissions in eBridge, travel arrangements and reimbursement, CVs, budgets, scheduling meetings and human resource matters. In addition, I serve as an Evacuation Marshall.
8701 Watertown Plank Road
Milwaukee, WI 53226
Ramchandran labMichelle Bordas, research technologist
I am interested in all aspects of animal care and research. My role in the lab is to maintain our mice colony. I maintain the colony in accordance with the guidelines and regulations for animal care use in research. Through my effort and those of other lab members, we are able to complete many valuable research projects while upholding the standards of best possible animal care. Together we are committed to the humane and appropriate use of animals for research.
Our lab had previously identified a long non-coding RNA anti-sense (AS) to tie-1 mRNA in zebrafish embryo. This long non-coding RNA, known as tie-1 AS, is conserved in human and mouse, and is implicated in human disease. We have also shown that tie-1 AS specifically regulates the expression of tie-1 mRNA. However, the exact mechanism of this regulation and the tie-1AS RNA function is unknown. Using molecular and developmental biology approaches, I am characterizing the function(s) and molecular mechanism(s) underlying the tie-1 AS RNA regulation of tie-1 during embryonic vascular development.
Dr. Shahram Eisa-Beygi, post-doctoral fellow
I am interested in identifying the mechanisms of neuro-vascular development, with a particular focus on the etiology of cerebral aneurysms, hemorrhagic strokes as well as vascular malformations of the brain, such arteriovenous malformations (AVMs) and cerebral cavernous malformations (CMMs). In particular, I am interested in elucidating the mechanisms of nascent blood vessel remodeling in response to mechanical cues. A thorough understanding of neurovascular development may help us design diagnostic tools and even identify potential therapeutic targets for CNS vascular malformations that present with high risk of hemorrhage.
Shubhangi Prabhudesai, PhD
I provide research support to the program in the field of neuroscience. I bring an interdisciplinary set of skills to the program, which includes zebrafish research and knowledge of neurobiology. I also manage the program’s day-to-day needs and supervise our zebrafish-facilities in Children’s Research Institute and MACC Fund Research Center. Finally, I collaborate with investigators both outside of MCW, and with program personnel on projects that are critical to the mission of the Developmental Vascular Biology program.
Emily Gronseth, graduate student
My research focuses on cancer metastasis, in particular the metastasis of medulloblastoma to extraneural locations. For my graduate work, I am specifically interested in the interaction between medulloblastoma tumors and astrocytes. Astrocytes are dynamic glial cells that comprise the majority of a medulloblastoma tumor microenvironment. I am currently working to determine the underlying mechanism(s) that cause astrocytes to induce medulloblastoma tumor cell invasion using in vitro techniques and an in vivo zebrafish xenotransplant model.
FacultyLing Wang, MD, PhD, instructor
My research interest is to understand the pathogenesis of cardiovascular disease and cancer, and applying this knowledge to treatment in the clinic. Currently, I am focused on elucidating the fundamental vasculogenesis mechanisms using a variety of cell culture, zebrafish and mouse models, and to explore the contribution of the vasculogenic process to tumor growth.
Erin Bishop, MD, assistant professor
The goal of my research is to determine the role ovarian cancer spheroids play in ovarian cancer metastasis and resistance to treatment. I am specifically focusing on the interactions between spheroids and the mesothelium by characterizing adhesion protein expression and function as well as the ability of spheroids to form tumors and respond to chemotherapy in vivo. A second project I am involved in describes the role of SNRK1 in ovarian cancer. As a gynecologic oncologist I take care of gynecologic oncology patients and plan to continue to combine my basic science experience and my clinical knowledge to work towards developing better treatments for gynecologic cancers.
Page updated 11/22/2017