Why can’t we regenerate the heart? A recent study by the Huang laboratory at UCSF explored the heart of echidnas, platypus, anteaters, armadillos, whales and bats, and identified a key hormone that made our ancestors warm-blooded but left us susceptible to heart damage.
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.
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.”
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.
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
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.
From the Dean
Dear School of Medicine Community,
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
Department of Pharmaceutical Chemistry, University of California, San Francisco
Despite significant advances in drug discovery over the past century, many disease-associated biomolecules remain challenging to target with “drug-like” small molecules. The Seiple group develops methods for the design, synthesis, and optimization of molecules that are larger and more structurally complex than traditional therapeutics.
Dr Pui-Yan Kwok has been elected by the Academia Sinica to its 2018 class of Academicians. A total of 21 academicians across all academic disciplines received this high honor this year. Academia Sinica is the national academy of Taiwan.
Kv7 channels are central to the control of excitation in the heart and brain, and harbor disease mutations associated with arrhythmias, epilepsy, and deafness. The calcium sensor protein calmodulin controls the action of Kv7 channels and provides a key link between channel activity and cellular signaling pathways. In this video, members from the Minor Lab describe their recent studies published in Neuron that uncover a universal mechanism by which calmodulin controls Kv7 channels through an Apo/CaM clamp and a C-lobe-driven switch mechanism.
Dear IHG Colleagues,
“I am writing to let you know that our esteemed colleague, Pui Kwok, will be assuming the directorship of the Institute for Biomedical Sciences at the Academia Sinica in Taipei, Taiwan, effective October 1. This is a tremendous honor, but also a great new opportunity for Pui to help build a large precision medicine program in Taiwan . . . he will maintain his lab and his significant roles in the IHG, namely as Director of the Genomics Core Facility, member of the Executive Committee, and co-Director of the Genomic Medicine Initiative. He will continue as co-PI on both the NBSeq study and the newly funded CSER2 program. He will also maintain roles within the CVRI and Department of Dermatology.
With his focus on precision medicine in Taiwan, we anticipate that there may be many opportunities for new collaborations between scientists there and here. . .
Let us all congratulate Pui on this recognition, and on the exciting opportunity ahead for him to build a new program to advance precision medicine and human genetics in Asia.”
Congratulatory message excerpts from Neil Risch, Ph.D., Director of the Institute of Human Genetics at UCSF.
As is being announced today at Novartis, Shaun Coughlin, MD, PhD, will be joining the biotech giant to become Global Head of Cardiovascular and Metabolism at Novartis Institute for Biomedical Research in Cambridge, Massachusetts. He will start his new position on November 1.
We are sad to lose one of our most respected leaders, yet profoundly grateful for his decades of service and immeasurable contributions to our mission. Dr. Coughlin is an outstanding example of the personal qualities that collectively have propelled UCSF to the top: a relentless drive to push the boundaries of our knowledge, a deep commitment to improve health for our patients, and steadfast devotion in teaching and mentoring the next generation of physician-scientists.
Dr. Coughlin received undergraduate and graduate training at Massachusetts Institute of Technology and an MD from Harvard Medical School. After an internal medicine residency at Massachusetts General Hospital, he joined UCSF for a cardiology fellowship and postdoc in 1984. He became a faculty member here in 1986, director of the Cardiovascular Research Institute at UCSF in 1997, and Distinguished Professor of Cardiovascular Biology and Medicine in 2006.
His research discoveries revealed a mechanism by which proteases regulate cellular behaviors including a key mechanism that controls blood platelet activation and clot formation. This work led to a new medical therapy for preventing heart attacks and strokes and has been honored by the American Heart Association’s Basic Science Award in 2003 and its Research Achievement Award in 2014. Among his numerous other awards are the Bristol-Myers Squibb Cardiovascular Research Award and the Distinguished Career Award from the International Society on Thrombosis and Haemostasis.
He is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts & Sciences.
CVRI Professor and Associate Director Brian Black, PhD, will be serving as interim director. A national search for a permanent new director will be initiated soon.
Shaun Coughlin’s impact on our institution has been invaluable. Please join me in thanking him for his service and wishing him the very best for his new career.
Talmadge E. King, Jr., MD
Dean, School of Medicine