Category: News and Events

$13 Million Grant to Probe the Genome of Heart Cells

The genome of human cells looks a lot like a tangled ball of yarn, with tightly wound clumps from which myriad loose strands escape and loop out. But there is order to this tangle, and growing evidence that the genome’s 3D architecture influences the activity of its genes.

Understanding the rules that control gene activity has been the object of a long collaboration between Gladstone Investigators Deepak Srivastava, Benoit Bruneau, Katherine Pollard, Bruce Conklin, and Nevan Krogan, and their UC San Francisco (UCSF) partner Brian Black. Together, they have already found many key regulators of gene activity in the heart.

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Golgi localized β1-adrenergic receptors stimulate Golgi PI4P hydrolysis by PLCε to regulate cardiac hypertrophy

Beta blockers are among the most widely used drugs for treating heart failure.  It has long been thought that these drugs act on proteins, known as adrenergic receptors, that solely reside on cell surfaces.  A recent study by scientists at CVRI and the University of Michigan has discovered a previously unknown role for adrenergic receptors within cells. When beta blockers were developed, there were no considerations for their abilities to access internal adrenergic receptors.  This new knowledge can potentially lead to the development of drugs that are more effective in the treatment of cardiovascular disease.


A Bullfrog’s Powerful Defense Against Toxic Red Tides


As climate change raises ocean temperatures, fisheries and public health agencies closely monitor the waters for harmful algal blooms known as red tides. The algae in these blooms produce a neurotoxin that accumulates in shellfish, rendering them dangerous, or even lethal, for human consumption. Bullfrogs, however, have a natural defense in the form of a protein known as saxiphilin.



How Scientists Detect the Most Lethal Shellfish Toxin You’ve Never Heard Of

There is a weapon that is released by algae around the world and concentrated, invisible, in the flesh of shellfish. An amount the size of a poppy seed is enough to kill a grown person. It’s part of an onslaught from which we’ve defended ourselves for decades, which might be why you’ve never heard of it.


Understanding the Language of Cells: A Look Inside the Jura Lab

The biochemists and structural biologists in the Jura Lab, which is affiliated with the Cardiovascular Research Institute (CVRI) and the UCSF Department of Cellular and Molecular Pharmacology, seek to understand what regulates how cells compute signals received from other cells or the environment to control cell growth and survival.

The lab, led by Natalia Jura, PhD, looks at how cells grow when they are healthy, and what goes wrong in diseases, such as cancer or neurodegenerative disorders. Signaling requires precise function of proteins, which often rely on phosphorylation/dephosphorylated cycle, a controlled process of addition and loss of a phosphate component. This cycle is orchestrated by enzymes called kinases that put on the phosphates and phosphatases that remove these modifications. “These are key enzymes that keep our tissues healthy,” said Jura. “Something happens to them – they change their protein structure due to a mutation, get abnormally activated or silenced, and then precise control of signaling pathways is gone. This then leads to disease because core functions of the cell, including decisions to survive, migrate, or die, are out of balance.”

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Frog Protein May Mitigate Dangers Posed by Toxic Marine Microbes Fueled by Climate Change

CVRI investigators have uncovered how an American bullfrog protein known as saxiphilin binds to and inhibits the action of saxitoxin. This deadly neurotoxin, which is about one thousand times more potent than cyanide, is made by algal blooms known as ‘red tide’. If ingested from contaminated shellfish, the toxin blocks electrical signaling in nerves and muscles, leading to death. Red tides are becoming more common due to climate change and these findings may lead to new ways to detect and neutralize the toxin.



Unique transmembrane domain interactions differentially modulate integrin αvβ3 and αIIbβ3 function

CVRI investigators decipher the mechanism by which platelets are activated to form clots, a key step in both normal and thrombotic processes. The researchers reveal how interactions between transmembrane helices of key proteins found in the membranes of platelets and many other cells help orchestrate the process. Their work is also informs our understanding of the assembly of many other proteins involved in transmembrane signal transduction.

Rustem I. Litvinov, Marco Mravic, Hua Zhu, John W. Weisel, William F. DeGrado, and Joel S. Bennett

PNAS paper

Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health

E-cigarettes are widely promoted as safer alternatives to cigarettes. But a new study by CVRI Center for Tobacco Control Research and Education’s Dharma Bhatta, PhD, and Stanton Glantz, PhD shows just the opposite. Using data from a large national survey, they found that both e-cigarettes and combustible cigarettes are independently associated with increased risk of myocardial infarction (heart attack). Significantly, they found that people who continued to smoke will using e-cigarettes (so-called “dual use,” the most common use pattern, was riskier than using either product alone and switching from combustible cigarettes to e-cigarettes is not associated with
lower risk of myocardial infarction than continuing to smoke. Complete cessation is the only way to reduce risk of myocardial infarction.

The conclude that e-cigarettes should not be promoted or prescribed as a less risky alternative to combustible cigarettes and should not be recommended for smoking cessation among people with or at risk of myocardial infarction.


JAHA Paper

Brian Black – Director of the Cardiovascular Research Institute Appointment

From the Dean



Dear School of Medicine Community,

I am pleased to announce the appointment of Brian L. Black, PhD as the new Director of the Cardiovascular Research Institute (CVRI), effective March 1, 2019.

Since joining UCSF in 1998, Dr. Black has led an internationally recognized basic research laboratory focused on developmental biology, with a primary emphasis on transcriptional control mechanisms. His research group has made several seminal contributions to the understanding of cardiovascular biology. Dr. Black has been part of CVRI leadership for the past 12 years and has served as Interim Director for the last 17 months.

Dr. Black earned his PhD in Microbiology and Immunology from Wake Forest University and conducted his postdoctoral training in Molecular Biology at the University of Texas Southwestern Medical Center in Dallas. Over the past decade, Dr. Black has served in leadership roles in the American Heart Association, the North American Vascular Biology Organization, and as a member the Weinstein Cardiovascular Development Steering Committee. He currently serves on the Editorial Board of the journal Development.

Dr. Black is a highly dedicated teacher and mentor at UCSF. He received the 2014 Haile T. Debas Excellence in Teaching Award for his efforts in medical student teaching. He has served as the CVRI mentoring program coordinator for the past 11 years and is the Principal Investigator of the CVRI’s postdoctoral training grant. Dr. Black is a member of the Biomedical Sciences and Developmental and Stem Cell Biology Graduate Program Executive Committees and currently serves on the Medical Scientist Training Program (MSTP) Council.

As a first-generation college graduate, Dr. Black brings an understanding that the path to higher education and to success in science may not be straightforward and that individuals, particularly those from underrepresented groups, often face obstacles along the way to success in science and medicine. He is committed to promoting the careers of women and individuals from groups that are underrepresented in science and medicine (UIM) and increasing the pipeline of female and UIM scientists as a source of future faculty members.

I am confident that Dr. Black’s vision and leadership will help maintain and expand the excellence of the science at the CVRI, while working to preserve the collegial and cohesive spirit that has made the Institute such a great place to teach, learn, and conduct research.

I would like to thank the search committee, chaired by Dr. Jeff Olgin, for its work in considering an exceptional pool of candidates from across the country for this position.

Talmadge E. King, Jr., MD
Dean, School of Medicine