Manuel Rosa-Garrido, PhD, Finalist for AHA Basic Research Prize
November 25, 2020
UCLA scientist Manuel Rosa-Garrido earned the honor of being one of only four finalists for the Louis N. and Arnold M. Katz Basic Research Prize at the American Heart Association (AHA) 2020 Scientific Sessions in November 2020 for his work on the development of heart failure. The Katz award competition is a high-profile event in the basic and translational science programming of the AHA meeting each year, showcasing outstanding science done by promising young investigators.
Heart failure results from a combination of genetic predisposition and environmental stress. Genetic predisposition is encoded in the genome and implies variation in underlying DNA sequences that alter gene expression. Environmental stress rarely modifies genetic sequence but can exert a powerful influence over gene activity through epigenetic programs. Dr. Rosa-Garrido's work has examined the influence of epigenetics in the setting of heart failure, towards the goal of developing new diagnostic tools and cures. To this end, he determined the folding principles of the genome in cardiac myocytes, determining the manner in which the actual structure of the DNA affects its expression in different cells.
Dr. Rosa-Garrido's current project expands his original work scope by including the study of DNA methylation and chromatin accessibility dynamics during development of heart failure. This new work shows an early epigenetic response to heart failure that includes widespread changes in DNA methylation and local chromatin accessibility, with important implications in determining the expression of several cardiac genes (e.g., Atp2a2, Nppa, Myh6, Tnni3) and non-coding RNAs.
Integrative analysis of these data with chromatin architectural information allowed Dr. Rosa-Garrido’s team to determine how changes in the methylation and accessibility status of enhancers, together with the presence of different cardiac transcription factors in regulatory regions, control the formation of enhancer-promoter interactions that govern gene expression. Temporal analysis of these epigenomic features also revealed how while DNA methylation changes detected during the late phase of heart failure are established early in pathology and conserved, changes in chromatin accessibility are primed during an earlier phase of heart failure and become amplified during pathology.
This project establishes that chromatin architectural reorganization participates in the setting of heart failure from the initial phases of pathology, and opens the possibility to use chromatin features to uncover early disease markers able to predict cardiac disease and to leverage direct targeting of chromatin structure as a heart failure therapy.
Collaborators on this project include lead author Douglas Chapski, PhD, and UCLA faculty Drs. Yibin Wang and Matteo Pellegrini. Dr. Rosa-Garrido’s research is supported by a grant from the American Heart Association. He is an assistant project scientist working on different epigenetic projects, all of which focus on studying how 3D structure of the genome changes during the development of heart failure.
--By Thomas Vondriska, PhD
Gregoire Ruffenach, PhD, wins AHA Career Development Award
July 15, 2020
Gregoire Ruffenach, PhD, a postdoctoral researcher in our department’s Division of Molecular Medicine, has won a prestigious Career Development Award from the American Heart Association in the amount of $231,000 for three years. Mansoureh Eghbali, PhD, the Director of the Basic Science Training Environment, serves as Dr. Ruffenach’s mentor for this award.
Dr. Ruffenach investigates the molecular mechanisms behind pulmonary hypertension (PH), a rare but serious disease that affects primarily women and carries a very poor prognosis. The life expectancy of patients with PPH is only about five years, and during that time patients have progressive decline in quality of life. Dr. Ruffenach is focusing on the role of post-transcriptional regulation of mRNAs in the development of pulmonary hypertension, with the end goal of developing new therapeutic approaches.
Congratulating Dr. Ruffenach, Dr. Eghbali said, “This award is a stepping-stone toward the transition of Dr. Ruffenach to be an independent researcher.”
Dr. Ruffenach began his postdoctoral fellowship in the Eghbali Laboratory in 2017. He earned his master’s degree and PhD degree abroad in France and Canada. Since joining our department, he has earned funding with two postdoctoral fellowships from the American Heart Association. In February, he received one of the prestigious UCLA Chancellor’s Awards for Postdoctoral Research.
Statin Usage is Linked to a Lower Death Rate in Hospitalized COVID-19 Patients
July 6, 2020
A new study led by Chinese researchers in collaboration with UCLA's Dr. Yibin Wang, PhD, has shown that people hospitalized with COVID-19 who took statin drugs were less likely to die and less likely to need mechanical ventilation than those who did not take the cholestorol-lowering drugs. Statin use also was linked to lower levels of inflammation, and a lower incidence of acute respiratory distress syndrome and admission to intensive care units. Read the full article here >
Christine Cunningham receives new award
June 12, 2020
PhD candidate Christine Cunningham from the Eghbali Lab won an award for her talk titled "Investigating the role of sex chromosomes in pulmonary hypertension—Y Not?" at the annual Molecular, Cellular & Integrative Physiology (MCIP) Departmental Retreat at Calamigos Ranch in Malibu on February 8th, 2020. After being nominated by the MCIP department, Christine was also recently awarded a Dissertation Year Fellowship from the UCLA Graduate Division. This merit-based fellowship covers stipend, tuition and fees during the last academic year of her PhD program.
Christine Cunningham receives Young Investigator Award
September 23, 2019
Christine Cunningham, a PhD candidate working with faculty mentor Mansoureh Eghbali, PhD, has been awarded the 2019 CTSI/Iris Cantor Women's Health Center Young Investigator Award for her exciting project, "Investigating Y chromosome protection against pulmonary hypertension as a novel therapeutic strategy for women". Pulmonary hypertension, or high blood pressure in the arteries of the lungs, is a potentially fatal disease that is difficult to treat and is more common in women for reasons that aren't yet fully understood.
CTSI, the UCLA Clinical and Translational Science Institute, supports training in multidisciplinary research and integrates community priorities into its goals. The Young Investigator Award is given only to one PhD candidate or post-doctoral student each year for research at UCLA related to women's health. Congratulations to Ms. Cunningham and Dr. Eghbali!
NIH R35 grant awarded to Riccardo Olcese, PhD
August 17, 2019
Riccardo Olcese, PhD, Professor of Anesthesiology and Physiology, has been awarded a prestigious 5-year MIRA R35 grant from the National Institute of General Medical Sciences.
This NIH award will continue to support his pioneering work on the molecular mechanisms controlling the voltage-dependent activation of calcium channels, fascinating macromolecules that convert electrical signals to calcium influx, initiating critical downstream physiological processes such as muscle contraction, neurotransmitter release and even gene regulation. R35 grants are Outstanding Investigator Awards that “provide long term support to an experienced investigator with an outstanding record of research productivity. This support is intended to encourage investigators to embark on long-term projects of unusual potential.
Dr. Olcese and his team will use electrophysiological, optical and computational techniques, including voltage-clamp fluorometry, to interrogate the macromolecular complex that constitutes the human calcium channel CaV1.1 and understand its function in the excitation-contraction mechanism of skeletal muscle.
This new knowledge is critical for understanding fundamental aspects of muscle physiology and the voltage-dependent control of contraction.
Varina Clark awarded Dean's Leadership in Health and Science Scholarship
March 29, 2019
Varina Clark, a 3rd year medical student in the David Geffen School of Medicine is the recipient of the competitive Dean’s Leadership in Health and Science Scholarship. She will receive funding to do a one-year fellowship in Dr. Soban Umar's lab in the Department's Division of Molecular Medicine. Her translational research project is focused on the investigation of novel gene therapy for right ventricular failure in the context of pulmonary arterial hypertension. The committee was impressed with the quality of her project, and the strength of the mentoring relationship between Dr. Umar and Ms. Clark described. After the fellowship, she will resume her medical school training as a 4th year medical student.
"Heart to Heart" event highlights UCLA research on role of sex hormones in heart disease
March 29, 2019
Mansoureh Eghbali, PhD, our department’s Director of Physician-Scientist Training and the Basic Science Research Training Environment, and UCLA graduate student Christine Cunningham were featured speakers at the recent “Heart to Heart” symposium in La Jolla, which focused on cardiovascular disease in women and on promoting heart health in California communities.
The event was part of the American Heart Association (AHA) celebration of “American Heart Month”, and was co-sponsored by the private, nonprofit National University System. Participants – speakers and audience members alike – wore red in support of the AHA’s “Go Red for Women” campaign to raise awareness and prevent heart disease and stroke in women.
Dr. Eghbali’s primary research interest has long been the molecular basis of the remodeling of voltage-activated K+ channels in the heart by sex hormones. She discussed her work searching for biomarkers to enable the early diagnosis of pulmonary hypertension, which is more common in women, and also pointed out the increased severity and occurrence rate of heart attacks in pregnant women.
Dr. Eghbali explained to the audience how UCLA’s innovative programs in precision health and genomics are spearheading a project to obtain blood samples from pregnant women with and without pregnancy complications. The results obtained from analysis of these blood samples, researchers hope, will improve physician ability to predict future complications from cardiovascular disease during pregnancy.
Ms. Cunningham, an award-winning PhD candidate, explained how sex chromosomes can influence both the risk of heart disease and the prognosis. She discussed how epigenetic modifiers encoded by women’s sex hormones may prove to be novel therapeutic targets for treating pulmonary hypertension. Both her work and Dr. Eghbali’s research are funded by AHA grants.
Christina Adams, MD, a cardiologist at Scripps Women’s Heart Center, spoke about ways that women can know more about their risks of heart disease, and how this knowledge may help in the effort to reduce risk factors. She stressed the importance of knowing the symptoms of heart disease, and recommended women to “know your numbers” – referring to blood pressure and lipid levels, especially HDL and LDL. She posed questions to the audience, asking them to consider “What is optimal health?” and “What is your most valued commodity?” Many women, she pointed out, know more about their husband’s and children's health than about their own.
One heart disease survivor, Donna Marie Robinson, told her own dramatic story of minimizing symptoms until she developed frank congestive heart failure. Even after she fainted during her spinning class, her symptoms were at first attributed to vertigo. After her diagnosis, she left a high-powered career as a banking executive to focus on her health and reduce stress with yoga and meditation. Her story serves as a cautionary tale of how women may not fit the expected mold of a “typical” heart disease patient, but they may still be at risk.
The “Heart to Heart” event on women’s heart health owed its success to the enthusiastic support of Michael Cunningham, PhD, the Chancellor of National University, and Jennifer Sobotka, the Executive Director at American Heart Association/American Stroke Association for the Greater San Diego Area.
Christine Cunningham contributed to the content of this article.
Fire damages research offices, computers
February 1, 2019
There’s never a good time to hear bad news, but two days before an American Heart Association (AHA) grant deadline is certainly on the more painful end of the spectrum. Especially when that news is that your office has caught fire. And the flames have taken your backups with them.
Such was the news that Michaela Ottolia, PhD, woke up to in the early morning on July 10, when phone calls from Business Office Manager Laura Benscoter and Interim Chair Barbara Van de Wiele, MD, alerted her to an electrical fire that had severely damaged her office, as well as Dr. Soban Umar’s office next door. In addition, the corridor was soaked by sprinklers and stained with smoke, affecting the air quality and working conditions for students, scientists and administrators in the research area of the Division on Molecular Medicine in the Center for Health Sciences (CHS).
“When I saw it, my first fear was about injury to anyone,” Dr. Ottolia said. But after she was reassured that no one was hurt, she immediately began to worry about the impending AGA Postdoctoral Fellowship grant deadline for her research fellow, Namuna Panday, PhD.
“The submission was due in two days! The finalized files were lost, together with my PC and laptop,” Dr. Ottolia recalled.
Ms. Benscoter kicked into even higher gear than usual and coordinated the efforts of multiple UCLA teams. The UCLA firefighters’ fast action quickly extinguished the fire, but water and smoke damage to documents and books had to be remedied by an outside document restoration firm. A team from DGIT (David Geffen Information Technology) was able to restore Dr. Ottolia’s computer files quickly. Facilities Project Manager Roland Amrhein led the thorough investigation and construction efforts.
Fortunately, the fire was confined to office space, and the laboratory teams were able to continue their experiments without interruption. Dr. Ottolia and her team lost little time on their research and grant submissions. She credits Ms. Benscoter, working with staff members Brianna Vidales and Nancy Cao, for making sure she had everything necessary to continue her work.
The administrative team, including CFO Wendy Ma and Administrative Specialist Jose Morales, made sure the AHA application was submitted on time. And in November, it was announced that Dr. Panday was awarded the grant. Dr. Ottolia also faced a second deadline two weeks after the fire, for a grant application (NIH Two-PI RO1) with Joshua Goldhaber, MD, a cardiologist at Cedars-Sinai Medical Center.
“I am happy to say this application received an excellent score and will likely be funded. So, in spite of the disaster, we managed to successfully move forward with our research work,” Dr. Ottolia said.
Could there even be a silver lining to the events of that morning in July? The fire interrupted not only her work, noted Dr. Ottolia, but the work of everyone in the department. However, the kindness, support and teamwork she experienced made her appreciate the department community even more. At the time of the fire, Dr. Van de Wiele had just been appointed Interim Chair.
“I am sure that a fire in the department was not on her agenda! It was very comforting to talk to her the morning of the fire and be assured of the department support in the recovery process,” Dr. Ottolia said. “It is especially during these stressful, unexpected events that we understand and appreciate expert and thoughtful leadership.”
Dr. Soban Umar's mentees take top honors at 2018 UCLA Cardiovascular Symposium
January 29, 2019
At the 2018 UCLA Cardiovascular Theme Symposium, Christian Makar (center) received the top award for an undergraduate research poster, and Christine Cunningham (right) won first place in the graduate category. Ms. Cunningham is a PhD candidate working in the research lab of Mansoureh Eghbali, PhD. Both students were mentored by Soban Umar, MD, PhD (left). Congratulations!
Manuel Rosa-Garrido, PhD, Wins AHA Early Career Award
September 19, 2018
Congratulations to Manuel Rosa-Garrido, PhD, who is honored with this year’s prestigious American Heart Association Outstanding Early Career Investigator Award. Dr. Rosa-Garrido, Assistant Project Scientist in the UCLA laboratory headed by Thomas Vondriska, PhD, was recognized both for the quality of his presentation and the potential impact of his work, “Elucidation of Gene Regulation Paradigms by Integrating Chromatin Architecture, Histone Marks, and DNA Methylation.” The award was presented at the Basic Cardiovascular Sciences 2018 Scientific Sessions in San Antonio, Texas.
The work studies “how the three dimensional structure of the genome changes during the development of heart failure and how these changes regulate the expression of the genes that trigger the disease,” says Dr. Rosa-Garrido. “We also found that cardiac-specific loss of the chromatin structural protein CTCF induces heart failure. Together, these findings suggest that remodeling is a promising target for therapeutic intervention.”
Dr. Rosa-Garrido is originally from the south of Spain and obtained his PhD in biomedicine from the University of Cantabria. There, he focused on ribosomal RNA transcription in cancer proliferation. He was recruited to the Vondriska Laboratory in 2012 as a postdoctoral fellow, where he shifted his focus to heart failure. The Vondriska Laboratory investigates the epigenomic mechanisms of cardiovascular disease.
After initially studying the reciprocal regulation of the cardiac epigenome, Dr. Rosa-Garrido’s current work focuses on how the 3D structure of the genome changes during the development of heart failure.
“The best part of working at UCLA is the work environment,” he says. “I have access to cutting-edge instrumentation and face-to-face interaction with experts in systems biology, epigenetics, and cardiology.” In addition, Dr. Vondriska’s support “has allowed me to develop my own project in a very independent manner and to share my work at national and international meetings: two essential elements for developing a successful career in research.”
Dr. Rosa-Garrido’s next step is to obtain research funding to facilitate his transition to principal investigator. “My ultimate career goal is to have my own research lab in academia where I can continue mentoring young scientists and improve the quality of life for patients with cardiovascular disease.”
Y Not? Our Research Team Studies Role of Y Chromosome in Pulmonary Hypertension
October 13, 2017
The first-ever study to shed light on the role of sex chromosomal influence on pulmonary hypertension appeared ahead of print on September 21 in the prominent American Journal of Respiratory and Critical Care Medicine. Our department’s researchers showed that the Y chromosome – found only in males – may be the single most important factor protecting against the development of this catastrophic disease.
The study – “The Y Chromosome Plays a Protective Role in Experimental Hypoxic Pulmonary Hypertension” – is the work of the cardiovascular research team headed by Soban Umar, MD, PhD, with the supervision and mentorship of senior author Mansoureh Eghbali, PhD.
Their work “will change the way we look at sexual dimorphism in pulmonary hypertension,” said Dr. Umar, adding that the article is accompanied by an editorial written by experts in the field.
The editorial noted that pulmonary arterial hypertension (PAH), a progressive and often fatal disease, is more common in females. Yet female patients seem to have a possible, poorly understood, survival advantage compared to males. The authors commented, “Determining the contributions of sex hormones versus sex chromosomes in experimental and human conditions is complicated, since they are intimately linked—the sex chromosomes influence the types, and levels, of sex hormones.”
The work of Drs. Umar and Eghbali explores the significance of the sex hormone complement in hypoxia-induced PAH, and found that XY mice develop less severe disease. The presence of the Y chromosome is the apparent source of protection.
Their article concludes, “A protective effect of the Y chromosome might help explain why male sex is the single best deterrent for developing PAH. Y chromosome genes expressed in the lungs could serve as novel therapeutic targets for PH treatment.”
It remains to be seen what specific genetic factors drive the Y chromosome’s influence, the editorial writers noted, and future studies will need to account for the role of sex hormones, the sex chromosome complement, and their interaction.
Dr. Umar’s research was supported by an American Thoracic Society Proof of Concept grant, and a recent UCLA Cardiovascular Theme Innovation Award will make the next phase of the study possible.
The Vondriska Lab Publishes New Findings on Links Between Heart Failure and DNA Modifications
September 8, 2017
The Vondriska Laboratory published new findings in the journal Circulation. The latest work of Manuel Rosa-Garrido, postdoctoral fellow; Douglas Chapski, graduate student; and Thomas Vondriska, PhD, UCLA professor of anesthesiology, medicine and physiology, links heart failure to modifications of how DNA is packaged within heart cells and challenges common theories on how heart disease develops.
“This study tells us that simply changing the way genes are packed together — even by a little bit — can have a widespread effect on the functioning of cells,” Vondriska said in an interview with the UCLA Newsroom. "This observation suggests treatments that restore the right arrangement of the chromatin might be able to restore proper genome-wide functioning," he said. “This is startling and quite exciting because it allows us to challenge assumptions about how cells work and about what causes disease — in this case, heart failure, which affects over 5 million Americans." Read the findings here.
UCLA Distinguished Cardiovascular Seminar Series
August 8, 2017
We are pleased to announce that the UCLA Distinguished Cardiovascular Seminar Series will be organized by Drs. Michela Ottolia and Gentian Lluri.
Michela Ottolia, PhD, is an Associate Professor in the Department of Anesthesiology and Perioperative Medicine. She completed her graduate studies in Biology at the University of Genoa, Italy, and trained as postdoctoral fellow at Baylor College of Medicine in Houston and later at UCLA in the field of Physiology and Biophysics of ion channels and transporters.
Dr. Ottolia was Associate Professor of Medicine and Biomedical Science at the Heart Institute of Cedars Sinai Medical Institute until 2017, when she was recruited to establish her laboratory in the Division of Molecular Medicine here at UCLA.
Dr. Ottolia’s current research interests lie in the areas of cellular electrophysiology, cardiac physiology and calcium homeostasis, focusing on molecular physiology of channels and transporters and their role in cell excitability in healthy and diseased hearts. Dr. Ottolia has authored numerous high impact publications and book chapters in the aforementioned topics and received grants from various funding agencies, including the National Institute of Health and the American Heart Association, where she also serves as a member of the grant review committee.
Gentian Lluri, MD, PhD, is an Assistant Professor of Medicine and Member of the Ahmanson/UCLA Adult Congenital Heart Disease Center. He received his MD and PhD degrees from the University of Vermont, College of Medicine where he focused on developmental biology for his graduate studies, followed by internal medicine residency at University of Illinois at Chicago. In 2011, he joined the STAR (Specialized Training Advanced Research) program at UCLA and completed his adult cardiology fellowship training and his post-doc with a focus in cardiac development. Next, he completed a two-year fellowship in adult congenital heart disease at UCLA and began his career as a physician scientist.
Dr. Lluri has a longstanding interest in molecular biological pathways that guide cardiac development and the disturbances of these pathways that can lead to cardiac malformations as well as calcification and fibrosis which affect the vast majority of patients with congenital heart disease.
Please join us in thanking Drs. Ottolia and Lluri for taking on this important responsibility, and contact them directly with any suggestions for invited speakers in 2018 and beyond. We also wish to thank to Dr. Arjun Deb for his dedicated leadership of this lecture series over the past few years.