Council

William A. (Bill) Muller, MD, PhD received his A.B. degree summa cum laude from Harvard University in 1975.  He earned his PhD degree from The Rockefeller University in 1981 under the mentorship of Drs. Ralph Steinman and Zanvil Cohn.  He received his MD degree in 1982 from Cornell University Medical College as part of the combined MD/PhD program.  After internship in Internal Medicine at Massachusetts General Hospital, he moved to the Brigham and Women’s Hospital in Boston for a combined residency/research fellowship program, which he completed in 1987.  Bill was recruited back to The Rockefeller University in 1987 as an Assistant Professor in the Cohn/Steinman lab with an adjunct position in the Department of Pathology at Cornell Medical School.  He was promoted to Associate Professor in 1994.  In 1997 he was recruited over to Cornell as Associate Professor with Tenure and subsequently promoted to Professor of Pathology in 2001.  In 2007 he was recruited to Northwestern as the Magerstadt Professor and Chairman of the Department of Pathology.  In 2016 he stepped down as Chair and has been focusing on expanding his research endeavors.

Dr. Muller’s research focuses on the cellular and molecular basis of the inflammation, and in particular the interactions of leukocytes and endothelial cells in the inflammatory response.  His lab first identified the critical roles for platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and CD99 in transendothelial migration, the process by which leukocytes cross blood vessels to enter the site of inflammation.  This demonstrated that transmigration was an independently regulated step in inflammation and defined molecular targets for anti-inflammatory therapy.  More recently his laboratory discovered a novel organelle in endothelial cells, the lateral border recycling compartment (LBRC).  This parajunctional membrane reticulum is distinct from other known endocytic compartments.  It contains PECAM, CD99, and other molecules required for transendothelial migration.  It is recruited to surround leukocytes as they pass across the endothelial cell and this recruitment appears to be the sine qua non for transendothelial migration.  The LBRC represents an important new element in the regulation of inflammation.

Dr. Muller’s research has been well funded by the National Institutes of Health, the American Heart Association, and several biotech companies.  He was the recipient of an American Heart Association Established Investigator Award and of the prestigious MERIT Award from the NIH.  Most recently, he received an R35 Outstanding Investigator Award from the NHLBI.  He is one of the Editors of The Journal of Experimental Medicine.  He was elected to membership in the Faculty of 1000 and the Henry Kunkel Society.  Other honors in the field of experimental pathology include election as a Fellow of the American Academy for the Advancement of Science (AAAS, 2010), the Rous-Whipple Award from the American Society for Investigative Pathology (ASIP, 2013), and the Ramzi Cotran Memorial Lecture (2014), and election to the Association of American Physicians in 2021.

Bill Muller has served in many official capacities over the years for the American Society for Investigative Pathology as well as for the North American Vascular Biology Organization (NAVBO) and was elected President of NAVBO in 2004.  He was Chairman of the ASIP Research and Science Policy Committee from 2016 – 2020, and was elected to the Presidential line of succession of the ASIP in 2020. 

Sophie Astrof received her Bachelor’s and Master’s degrees in Biochemistry from Brandeis University in 1995 in the laboratory of Dr. Abeles. She received her Ph.D. degree in Virology from Harvard University in 2000 in the laboratory of Dr. John A.T. Young. Consequently, she did her postdoctoral work with Dr. RIchard Hynes at MIT where she developed her interest in extracellular matrix biology and cardiovascular development. Astrof lab investigates mechanisms by which cell-extracellular matrix interactions orchestrate cardiovascular development and how alterations in these interactions cause congenital heart disease.

Dr. Mingxia Gu is an Assistant Professor of Pediatrics at Cincinnati Children’s Hospital Medical Center. Dr. Gu received her M.D. from Peking University in Beijing, China, and attended a joint-training Ph.D. program at Peking University and Stanford University in the laboratory of Dr. Joseph Wu. She then stayed at Stanford as an AHA fellow in Dr. Marlene Rabinovitch's lab. In 2016, Mingxia joined Pediatric Cardiology at Stanford Lucile Packard Children’s Hospital (LPCH) as an Instructor with a K99/R00 award. In early 2020, Mingxia moved to Cincinnati Children’s Hospital Medical Center with joint appointments in the Center for Stem Cell & Organoid Medicine (CuSTOM), and Divisions of Pulmonary Biology, Molecular Cardiovascular Biology, and Developmental Biology. The overarching goal of the Gu lab at Cincinnati is to understand the signaling driving tissue-specific endothelial cell fate commitment, and to develop novel therapeutic strategies for the regeneration of the vascular beds in congenital heart and lung defects.

Inflammation in vascular disease
The primary cause of cardiovascular disease is a chronic inflammatory disease called atherosclerosis. Inflammation changes the cellular composition of the blood vessel wall, essentially caused by a buildup of cellular material, which blocks blood flow. This can lead to major adverse complications including thrombosis, stroke and death. Cell signaling is a key regulator of the inflammatory process within the blood vessels. The Johnstone Lab's research focuses on the identification of cell signaling pathways that could provide a better understanding of the underlying causes of cardiovascular disease.

Proliferation in vascular disease
Treating arterial blockages in patients involves either grafting of blood vessels to bypass the blockage (coronary artery bypass) or implanting support structures called “stents” in the vessel to open up the blood flow. A significant side effect of each of these treatments is that cells start to divide inside the blood vessel wall, blocking the artery once again. The lab's research aims to identify new pathways that specifically regulate this process to help us understand the disease and to allow for the development of targeted therapeutics.

Connexin proteins, gap junctions and therapeutics
Cells communicate in a vast array of ways. The primary source of direct cell-to-cell communication occurs through gap junction channels comprised of connexin proteins. In addition to their well-established role in coordinating tissue functions, research by our group and others has shown that these are highly diverse proteins, which regulate cell functions through direct protein-protein interactions. Our lab focuses on identifying novel pathways involved in the formation of these interactions and ways in which we can manipulate these to disrupt diseased cell functions. Currently, the Johnstone Lab is developing a range of peptide-inhibitors which show promise in reducing cell proliferation in vivo and for future development to small molecules drugs.

Pannexin channels
Identified in 2000, this new class of purine (e.g. ATP) release channels have can control multiple cellular and tissue functions. Our research pinpoints that pannexin channels allow for a diverse array of signaling events within the vasculature, controlling normal physiological processes such as blood vessel tone to pathological vascular inflammation. However, signaling regulation via these channels is still poorly understood. The lab aims to define new molecular signaling pathways regulated by this class of membrane proteins. Its goal is to understand how these proteins are regulated from transcription to translation, and to identify channel functions in vascular physiology and pathophysiology.

Additional research
There are common pathways in vascular disease, cancer and wound healing. These include the role for inflammation, cell signaling and cellular proliferation. Currently, the Johnstone Lab is working with multiple groups to investigate parallel pathways which can be exploited to reduce proliferation in cancer cells and to promote wound healing with reduced scar formation.

Bernadette has been the Executive Officer of NAVBO since 2007.  Prior to that she was the Administrator from 1994 and has been with NAVBO since its inception.