Grants and Awards

Funding Years: 2021 – 2026

Funding Years: 2008 – 2024

Heart attack and its complications comprise a global health problem for which there are few highly effective treatments. As an innovative therapy, this proposal seeks to amplify the body's native repair machinery by stimulating vascular progenitor cells in the bone marrow and then specifically directing them to the heart to grow new perfusing blood vessels to the damaged heart muscle and providing a clinically viable treatment for human disease.

Dr. Hanjay Wang is currently a 5th year resident in the Integrated Cardiothoracic Surgery Residency Program. He has spent the last three years as a postdoctoral research fellow in Dr. Joseph Woo's laboratory, focusing on heart regeneration mechanisms in neonatal and adult mammals, as well as the impact of myocardial, vascular, and valvular biomechanics on surgical outcomes.

Funding Year: 2018 – 2020

Through a seed grant from the Stanford Cardiovascular Institute, Hanjay is working with Dr. Jack Boyd on developing a biodegradable device to stabilize vein graft biomechanics and improve patency rates after coronary artery bypass grafting.

Hanjay was awarded the Council on Cardiovascular Surgery and Anesthesia Resident Prize at the American Heart Association’s Scientific Sessions 2018 in Chicago, IL. Dr. Wang presented his research entitled “Computationally-Engineered Analog of Stromal Cell-Derived Factor 1α Preserves the Mechanical Properties of Infarcted Myocardium Under Planar Biaxial Tension” in an oral abstract competition for a panel of judges and received his award from AHA president Dr. Ivor J. Benjamin and CVSA chair Dr. Jennifer Lawton. (November 2018)

Funding Years: 2019 – 2021

Yuanjia was awarded the Thoracic Surgery Foundation Resident Research Fellowship for her project titled "Bioengineered Autologous Cytokine-eluting Arterialized Conduits using Tri-Layered Cell Sheet Technology." This two-year grant is administered through The Thoracic Surgery Foundation. The proposed project focuses on bioengineering a novel, autologous, cytokine-eluting, arterialized vessel conduit using cell sheet technology. Yuanjia proposed to characterize in vivo efficacy and investigate the impact of the bioengineered conduit in a rodent hindlimb ischemia model. The results from this study may guide researchers and healthcare providers towards a novel, translatable revascularization therapy.

Award Year: 2020

The TSDA Benson R. Wilcox Award was established in 2010 to acknowledge the best scientific abstract submitted by a cardiothoracic surgery resident to The Society of Thoracic Surgeons Annual Meeting. This annual award honors Dr. Wilcox’s many contributions to the TSDA and thoracic surgery education.

Dr. Zhu recieved the award for Bilateral versus Single Internal Mammary Artery Grafts for Coronary Artery Bypass Surgery in the United States – A Study of Over One Million Patients

• American Heart Association BCVS Minority Travel Grant

Funding Year: 2019

Project title: Neuregulin-1 Promotes Cardiomyocyte Survival and Proliferation Under In Vitro Conditions of Hypoxic Hyperglycemic Stress.

Cardiomyocytes were pretreated with either saline or Neuregulin-1 in hyperglycemic and euglycemic solutions. We found that Neuregulin-1 signaling is reproduced in hypoxic and hyperglycemic conditions and can be used for further optimization studies.

Funding Year: 2018

Project title: Minimally Invasive Delivery of Engineered Stromal-Cell Derived Factor 1-alpha via Hydrogel Limits Left Ventricular Negative Remodeling Following Myocardial Infarction.

After permanent ligation of the left anterior descending coronary artery, Sprague-Dawley rats were treated with saline, ESA or ESA in a hydrogel. We found that ESA delivered in a hydrogel provided sustained release and limited left ventricular deterioration.

During the Meharry Medical College 62nd Annual Student Research Day, MS2 students presented their summer research to their peers and a panel of judges in each of the following categories: Basic Science Research, Translation Research and Clinical Research. An award of first, second or third place were given to students with the best presentations in their respective category. (May 2018)

Funding Years (combined with the SGF grant): 2016/17 – 2020/21

The National Science Foundation (NSF) Graduate Research Fellowship Program recognizes and supports outstanding graduate students in NSF-supported STEM disciplines who are pursuing research-based master's and doctoral degrees at accredited US institutions. The five-year fellowship includes three years of financial support.

Annabel's research statement for this fellowship was based on her senior thesis, entitled "Designing an Implantable Cardiac Perfusion Monitor." It is not expected that students applying in college actually continue with the research they propose in the application, and Annabel has since pivoted to other work.

Funding Years (combined with the NSF grant): 2016/17 – 2020/21

The multi-year Stanford Graduate Fellowship in Science and Engineering (SGF) supports exceptional incoming and continuing doctoral students in the natural and social sciences, education, engineering, and the basic sciences in the School of Medicine.

Annabel was nominated by her department based on the strength of her application to the graduate program, and the 3-year fellowship was awarded after her senior year of college.

Funding Years: 2015-2018

The NSF Graduate Research Fellowship Program recognizes and supports outstanding graduate students in NSF-supported STEM disciplines who are pursuing research-based master's and doctoral degrees at accredited US institutions.

Lyndsay's application was about studying tumor growth and 3D cell culture application.

Funding Years: 2018-2020

The AHA Predoctoral Fellowship is awarded to enhance the integrated research and clinical training of promising students who are matriculated in pre-doctoral or clinical health professional degree training programs and who intend careers as scientists, physician-scientists or other clinician-scientists, or related careers aimed at improving global cardiovascular, cerebrovascular and brain health.

Lyndsay's application was based on post operative adhesions in the cardiac space specifically.

Funding Years: 2018–2020

The Stanford Bio-X Graduate Fellowships offer Ph.D. candidates funding independent of any one lab or grant, freeing recipients to pursue interdisciplinary research and to work with multiple mentors.

The Stanford Interdisciplinary Graduate Fellowship (SIGF) Program is a competitive, university-wide program that awards three-year fellowships to outstanding doctoral students engaged in interdisciplinary research. The SIGF supports Stanford doctoral students in undertaking novel, cutting-edge research and pursuing questions that cross traditional disciplinary boundaries.

Lyndsay's application was based on post operative adhesions.

Kiah is a fourth year medical student at Stanford. She has worked in the Woo lab during medical school to study heart failure therapeutics in various animal models. Specifically, she has investigated how photosynthetic bacteria may be used to treat cardiac ischemia.

Award Year: Spring 2018 – Spring 2019

Since 1980, the Stanford Medical Scholars Research Program has supported medical student research, both locally and off-site. Students carry out research in an academic setting under the direction of faculty members here at the medical school, hospital and clinics, and throughout the University.  

For this grant, Kiah had to submit a detailed proposal of her project and a letter of support, which were then reviewed by the MedScholars committee. 

The work Kiah completed with this funding was recently published in Microbial Biotechnology, and she presented it at the MedScholars Research Symposium.

Award Year: July 2020 – July 2021

The Stanford Maternal and Child Health Research Institute (MCHRI) Pilot Grants funds innovative maternal and child health-focused clinical and translational research.

• NIH KL2 Mentored Career Development Program
  

Funding Years: Awarded Fall 2019, and runs through Fall 2021

Project Title: "Optimization of Surgical Repair Strategies in an Ex Vivo Model of Single Ventricle Physiology."

Project Abstract: Single ventricle defects are rare congenital disorders that affect one of the two ventricles of the heart, leading to one of them being undersized, underdeveloped, or missing a valve. These defects are fatal without surgical intervention, and surgeries typically need to be performed soon after birth. Staged surgical repair is performed shortly after birth and involves the rerouting of blood flow into the stages of Single Ventricle Physiology (SVP), from Norwood, to Glenn, and ultimately, Fontan circulation. Although there are variations of this transition, it generally involves rerouting the inferior and superior vena cavae directly into the pulmonary arteries, and subsequently utilizing a single ventricle and atrioventricular (AV) valve to support systemic circulation. Atrioventricular (AV) valve function is an important component of this circulation, especially as the longevity of children palliated with SVP continues to rise. While many risk factors associated with SVP have been overcome, numerous clinical studies have shown increased morbidity and mortality associated with AV valve insufficiency. The purpose of this proposal is to study heart valve function in response to Single Ventricle Physiology (SVP), with the goal of learning how SVP affects valve biomechanics, fluid dynamics, and tissue changes at the molecular level.

Awarded to the Stanford Thoracic Surgery Clinical Research Program
PI: Joseph Shrager
Co-PI: Leah Backhus

Funding Year: 2019 – 2023

The Stanford Thoracic Surgery Clinical Research Program was awarded an NIH R01 titled: "A mechanistic clinical trial of JAK inhibition to prevent ventilator-induced diaphragm dysfunction." Ventilator-induced diaphragm dysfunction is a process in which the diaphragm (the major respiratory muscle) weakens and atrophies while a patient is on mechanical ventilation (MV). This can lead to prolonged need for the ventilator, resulting in increased complications (e.g., ventilator-associated pneumonia) and deaths. The long-term goal of this program has been to develop/identify a drug that could be used to prevent this process and thus reduce ICU morbidity/mortality. The program worked out the molecular mechanisms underlying the process in human tissue from mechanically ventilated patients and in animal MV experiments. One molecular pathway we identified as being important is the JAK/Stat pathway. In this NIH-funded clinical trial, they are randomizing patients to a JAK inhibitor (Tofacitinib) vs placebo and then taking diaphragm biopsies early and late (about 6 hours apart) during esophagectomies. They are then studying the biopsies to assess for whether they have successfully blocked the involved pathways and for whether they have prevented the onset of diaphragm weakness (using a single-fiber muscle force transduction device).

Awarded for: "iSALT: Imaging Surveillance After Lung Cancer Treatment" - VA HSR&D IIR Merit Award (HX002456-01A2)

Principal Investigator: Dr. Leah Backhus

The VA Health Services Research & Development Investigator-Initiated Research program enables VA clinicians and social scientists to pursue their personal research interests while advancing HSR&D priorities and contributing to the quality, effectiveness, and efficiency of VA health care. The IIR program spans the traditional, enduring areas of health services research (cost, quality, and access) as well as emerging areas and current topics (e.g., patient safety). Most projects are multidisciplinary in nature, involving a team of researchers with expertise in a variety of clinical specialties and academic disciplines. Many IIR studies involve data collection at multiple sites, to enhance generalizability and eventual dissemination. Rigorous scientific and programmatic review ensures the high quality of IIR research, and funding is highly competitive. All proposals undergo peer review by an interdisciplinary group of VA- and non-VA researchers. Recommendations of the Scientific Review and Evaluation Board regarding a project's scientific/technical merit, as well as importance to VA, inform all IIR funding decisions.

The Dr. Dwight C. McGoon Award is an award given annually by the TSRA to an outstanding young faculty member in cardiothoracic surgery in recognition of his or her commitment to resident education and mentorship. Each year, cardiothoracic surgery residents in North America are eligible to nominate a faculty member within the first ten years of their attendingship who has demonstrated a remarkable interest in resident training — inside or outside of the operating room. From the nominated faculty, the winner will be selected and presented with the award at the STS Annual Meeting.

Dr. Leah Backhus is the first woman to receive the award in fourteen years, the first African American recipient, and the first recipient from Stanford.

Funding Year: 2019

The Levi Watkins Innovation and Leadership Development Scholarship provides up to $5,000 for cardiothoracic surgeons who are within 10 years of their first faculty appointment and supports travel to a center of excellence for the purposes of acquiring clinical, translational, or leadership training.

TSF awarded the Watkins scholarship to Dr. Backhus in 2019. In November, she traveled to the Mayo Clinic in Phoenix, Arizona, where she studied pectus repair with Dawn Jaroszewski, MD, MBA, a national leader in surgery for pectus carinatum, excavatum, and mixed defects in adults.

Dr. Leah Backhus, co-director of the Stanford Thoracic Surgery Clinical Research Program, on winning the award: "My goal in pursuing this scholarship was to gain experience in a variety of repair techniques by visiting a high-volume center performing minimally invasive adult pectus surgery and complex reconstructions,” she said. “As the final goal is to establish a program at my home institution, it was important to also gain experience with patient selection and program infrastructure."

The Dr. Dwight C. McGoon Award is an award given annually by the TSRA to an outstanding young faculty member in cardiothoracic surgery in recognition of his or her commitment to resident education and mentorship. Each year, cardiothoracic surgery residents in North America are eligible to nominate a faculty member within the first ten years of their attendingship who has demonstrated a remarkable interest in resident training — inside or outside of the operating room. From the nominated faculty, the winner will be selected and presented with the award at the STS Annual Meeting.

Dr. Natalie Lui is the second woman to receive the award in fourteen years, and Stanford is one of only two institutions to recieve this award twice.

• Western Thoracic Surgical Association Donald B. Doty Educational Award 2019
  

"3D printing for cardiothoracic surgical education: a mediastinoscopy model"

• Stanford Clinical Innovation Fund 2019

"Identifying barriers to lung cancer screening enrollment"

• The Thoracic Surgery Foundation Carolyn E. Reed Traveling Fellowship Award 2018

"Advanced endoscopic techniques for esophageal disease at the Oregon Clinic"

Funding Year: 2020

John was accepted into the Human Biology Honors Program and awarded the VPUE Major Grant from the office of the Vice Provost for Undergraduate Education. The Major Grant is a 10-week stipend in support of full-time immersive summer project/research commitments. This summer John is conducting a retrospective patient chart review to access the potential benefits of pairing mammography for breast cancer screening with effective outreach for low-dose CT scanning for lung cancer screening in eligible women in order to improve lung cancer outcomes.

Abstract: Starting at the age of 40 in the US, women begin to receive mammograms annually to screen for breast cancer. Lung cancer remains the most fatal cancer for men and women in the US. Although CT scanning for lung cancer screening (LCS) has been shown to lower the risk of death in current/former smokers by up to 20%, utilization of this service within the eligible population sits extremely low at 3.9%. Meanwhile, in a large national survey of older women, nearly 70% of the participants reported receiving mammograms for breast cancer screening within the past two years. There is a great opportunity among women who actively/previously smoke and are currently receiving radiology services to receive risk-reducing LCS services, however lack of access, education, awareness, anxiety, and outreach among eligible patients contribute to the low LCS rates. It remains to be determined whether annual or bi-annual LCS via low-dose CT scanning is a cost-effective and beneficial protocol for high-risk individuals. The purpose of this study is to assess the potential benefits of pairing mammography for breast cancer screening with effective outreach for low-dose CT scanning for lung cancer screening in eligible women

Funding Year: 2020

John was accepted into the Human Biology Honors Program and awarded the VPUE Major Grant from the office of the Vice Provost for Undergraduate Education. The Major Grant is a 10-week stipend in support of full-time immersive summer project/research commitments. This summer John is conducting a retrospective patient chart review to access the potential benefits of pairing mammography for breast cancer screening with effective outreach for low-dose CT scanning for lung cancer screening in eligible women in order to improve lung cancer outcomes.

Abstract: Starting at the age of 40 in the US, women begin to receive mammograms annually to screen for breast cancer. Lung cancer remains the most fatal cancer for men and women in the US. Although CT scanning for lung cancer screening (LCS) has been shown to lower the risk of death in current/former smokers by up to 20%, utilization of this service within the eligible population sits extremely low at 3.9%. Meanwhile, in a large national survey of older women, nearly 70% of the participants reported receiving mammograms for breast cancer screening within the past two years. There is a great opportunity among women who actively/previously smoke and are currently receiving radiology services to receive risk-reducing LCS services, however lack of access, education, awareness, anxiety, and outreach among eligible patients contribute to the low LCS rates. It remains to be determined whether annual or bi-annual LCS via low-dose CT scanning is a cost-effective and beneficial protocol for high-risk individuals. The purpose of this study is to assess the potential benefits of pairing mammography for breast cancer screening with effective outreach for low-dose CT scanning for lung cancer screening in eligible women

Thoracic aortic aneurysm is a potentially fatal disease, increases in frequency with age, and represents one of the 15 major causes of death in this county. Investigating mechanisms that cause aortic wall degeneration during aneurysm development will potentially open the door for innovative preventative approaches by providing new targets for therapeutic strategies. Discoveries from this project may translate into clinical practice and enhance the health of patients with aortic aneurysms. (May 2017)

A.J. Pedroza is a fourth year Cardiothoracic Surgery resident currently completing an NIH-funded research fellowship in the Thoracic Aortic Research Laboratory under the direction of Dr. Michael Fischbein. His research focuses on dynamic gene expression changes driving thoracic aortic aneurysm development and progression using genetic mouse models and human surgical tissues.

Funding Years: July 2020–June 2022

The Ruth L Kirchstein Postdoctoral Individual National Research Service Award is a federal award granted through the National Heart, Lung, and Blood Institute (NHLBI) within the National Institutes of Health (NIH) to enhance the research training of promising postdoctoral candidates who have the potential to become productive, independent investigators in scientific health-related research fields.

The two-year grant provides funding to continue research on developmental contributors to aortic smooth muscle cell pathology leading to aortic aneurysm development in Marfan syndrome, an inherited connective tissue disorder.

Dr. Alex Dalal is a third-year Integrated Stanford Cardiothoracic Surgery resident soon to begin his postdoctoral research fellowship in Dr. Michael Fischbein's lab.  Alex will be studying the molecular mechanisms of aneurysm formation in genetic aortopathies, such as Marfan Syndrome and Loeys-Dietz Syndrome. Alex previously spent two years working in Dr. Fischbein's lab as a lab tech prior to medical school and is excited to return to the lab as a resident.

• Stimulating Access to Research in Residency (StARR) NIH R38

Funding Year: 7/2020-7/2021

This is a twelve-month grant that will cover eighty percent of Alex's PGY salary during his postdoctoral research under the mentorship of Dr. Michael Fischbein. Alex is currently studying the molecular mechanism of aneurysm formation in Marfan Syndrome. Single cell RNA sequencing of Marfan Syndrome and Wild Type littermate control mouse aortas revealed a unique sub-set of smooth muscle cells, term fibroblast like smooth muscle cells (FL-SMCs), that are spatially unique to only the Marfan Syndrome ascending aorta. This grant proposal investigates the embryologic origin of the FL-SMCs and aims to determine the pathologic significance of FL-SMCs in Marfan Syndrome aneurysm development.

Joshua Orrick is currently a premed student studying human biology in Orange County, California. His concentration of study is neurobiology and neurological disorders; however, he has developed an overarching passion for studying cardiothoracic-related diseases through his time in Dr. Michael Fischbein's lab. In his spare time, Josh is on the Stanford varsity men's water polo team, and his team won a D1 NCAA national championship last season.

• Vice Provost for Undergraduate Education Major Grant

Funding Year: 2020

Josh is conducting his honors thesis on the effects of angiotensin-related drugs such as Losartan on Marfan's pathology within the Fischbein lab. He is currently being mentored by Dr. Michael Fischbein and Dr. Christiana Iosef.  The aim behind his project is to stop or slow the dilation of the aorta in Marfan Syndrome (MFS) patients with the use of these drugs. The mechanisms by which angiotensin-related drugs act to stop/slow aortic dilation are largely unknown; thus, Josh plans to use MFS smooth muscle cells derived from MFS patient-induced pluripotent stem cells to model and record the mechanisms.

Samantha "Sam" Churovich is a freshman undergraduate student at Stanford University and plans to major in human biology. For the past few years, Sam has the privilege of working as a research assistant in Dr. Michael Fischbein's Lab and within the Department of Cardiothoracic Surgery.

Funding Year: 2020

In April 2020, Sam was awarded the Stanford Cardiovascular Institute Summer Undergraduate Research Grant. This is a ten-week summer fellowship that will support her ability to continue conducting research with Dr. Michael Fischbein, ultimately presenting her progress and findings at the program's closing symposium. Working alongside Dr. Albert J. Pedroza, the most current research propelling her grant application has involved using single-cell RNA sequencing technology to analyze heterogenous populations within mutant and wild-type mouse aortas, as well as within Marfan-diagnosed patients undergoing reparative/treatment surgery.   

This award aims to foster the development of surgeon scientists in cardiothoracic surgery; increasing knowledge and innovation to benefit patient care. (July 2017)

Dr. Terrence Pong is a PGY3 in the Stanford Integrated Cardiothoracic Surgery residency program. Terrence completed his doctoral degree in Medical Engineering and Medical Physics (MEMP) at the Harvard-MIT program in Health Sciences and Technology (HST). His previous research has focused on implantable biosensors for the detection of cardiac biomarkers and the modulation of nitric oxide synthase for cardiac protection. He is currently conducting  his postdoctoral research in Dr. Anson Lee's Cardiac Surgical Arrhythmia Research Lab.

• Stanford Medicine Spectrum Biodesign Medtech Award

Funding Year: 8/2019 – 8/2020

Terrence's research interests focus on the design and engineering of surgical tools for advanced diagnostics and treatment of cardiac arrhythmias. Funding from the Stanford Biodesign award supports the development of a novel "System for transmural ablation of atrial fibrillation." In addition, Terrence will be conducting research on Experimental Heart Models of Ventricular Tachycardia through the generous support of the Steven M. Gootter Foundation.

Kevin Cyr is a 4^th year medical student at Stanford University School of Medicine. His research is focused on developing new surgical tools for the treatment of atrial fibrillation and other heart rhythm disorders in the laboratory of Dr. Anson Lee. These efforts have focused on translational research which brings 3D printing technologies into the operating room to create patient-specific surgical devices. His work to develop 3D printed medical devices has been recognized with grants and awards from the Society for Thoracic Surgery, Stanford Medical Student Research Symposium, Stanford Cardiovascular Institute., and Stanford Byers Center for Biodesign.

• Looking to the Future Scholarship

Funding Year: 2019

• Grand Prize Stanford Medical Student Research Symposium   

Funding Year: 2019

• Boring Trust iHeart Research

Funding Year: 2018 – 2019

• Stanford Biodesign NEXT Fellow
  

Funding Year: 2018

• MedScholars Medical Student Research Fellowship

Funding Year: 2018 – Present

The AIMI Seed Grant program seeks to stimulate and support the creation of innovative and high-impact ideas that will advance the fields of medicine & imaging. AIMI funds exciting and innovative projects based on their scientific merit, potential clinical impact, and alignment with program priorities.

Project title: "Automating the Analysis of Echocardiographic Images for Predicting Post-Operative Right Heart Failure"

PI: William Hiesinger, Jeffrey Teuteberg
Co-Investigators: Rohan Shad, Nick Quach, Patpilai Kasinpila

Predicting post-operative right ventricular failure (RVF) has proven challenging despite decades of research. We aim to use a neural network to segment transthoracic echocardiograms (TTEs) collected as part of standard clinical care. The segmented TTEs will be used for the extraction of novel RVF metrics that have shown promise in predicting post-operative RVF, which will then be used to generate predictive models that are both sensitive and specific for post-operative RVF. The outcome of this research project will be the creation of a validated, clinically translatable, end-to-end automated tool for predicting postoperative RVF in patients undergoing LVAD implant.

Cayley Bowles is currently a PGY-2 in the Stanford Integrated Cardiothoracic Surgery residency program and will be joining Dr. William Hiesinger's lab in July 2020. Cayley will focus on heart failure research using a variety of research methods. Her previous research has included differential equations-based models of infectious disease spread and computational models of the cardiovascular system. Cayley also completed a master's degree in epidemiology at the Harvard School of Public Health where she learned statistical techniques for outcomes research.

Funding Year: 7/2020-7/2021

Cayley was fortunate to receive funding from the Stimulating Access to Research in Residency (StARR) NIH R38 grant through the Stanford Cardiovascular Institute. This grant will fund her first research year and was awarded for a research project involving protein engineering to promote healing after myocardial infarction. Cayley will also plan to explore the use of machine learning to predict right heart failure in LVAD patients.

Nick Quach is a rising third-year medical student at Stanford working within Dr. William Hiesinger's lab.  Nick’s current research works to develop novel chemokine therapeutics for cardiac recovery in ischemic cardiomyopathy.  Additionally, Nick is working to create a new machine-learning based diagnostic tools for predicting postoperative outcomes.

Nick was awarded the Boring Trust Research Award in Sept 2019 by the Stanford Cardiovascular Institute to create new therapeutics by reengineering the angiogenic chemokine SDF-1a using computation methods.

Funding Year: 2019-2020

Nick was awarded the MedScholars Medical Student Research Fellowship in June 2019 by the Stanford School of Medicine to create new therapeutics by reengineering the angiogenic chemokine SDF-1a using computation methods.

Julian is a first-year medical student interested in a career in surgery, who joined the William Hiesinger Lab as a medical student researcher in 2020. He graduated from the University of Southern Maine with a degree in Biology in 2016 and spent the next three years volunteering and teaching English in Ecuador before joining the entering class of 2019 at Stanford Medical School.

Funding year: Summer 2020

Julian was recently awarded a Discovery Grant through the Medical Scholars Research Program, a program supporting medical student research since 1980. He will be supported by the grant during the summer of 2020, during which time he will be investigating the immunomodulatory role of the chemokine SDF-1α in the acute inflammatory response to ischemic coronary syndrome alongside the dedicated team of scientists at the William Hiesinger Lab.

This proposal aims to improve the clinical efficacy of iPSC-EC transplants through the design of a novel combinatorial family of engineered extracellular matrices (eECMs) with independently tunable biochemical and biomechanical cues to allow identification of optimal eECMs that promote iPSC-EC angiogenic potential. An in vitro array of 279 unique, combinatorial eECMs will be screened for enhancement of iPSC-EC viability, phenotype, and function, and optimal eECMs will be validated in a preclinical animal model of PAD. (April 2019)

This study examines the role of spatially patterned nano-scale biomaterials in enhancing the potential of stem cell-derived endothelial cells to survive and restore blood flow in the setting of peripheral arterial disease. The results of the proposed small and large animal studies will improve the efficacy stem cell therapy for treating peripheral arterial disease. (February 2018)

The goal of this project is to develop a tissue chip for high-throughput systematic control of ECM chemical composition, substrate stiffness, and mechanical stretch to identify microenvironmental conditions that optimize muscle progenitor cell survival, myotube formation, and contractility. (July 2019)

We propose to engineer a murine skeletal muscle tissue containing both muscle and vascular cells for treatment of acute volumetric muscle loss in a murine model. (April 2019)

The goal of this study is to test the efficacy of engineered skeletal muscle in microgravity to resemble salient characteristics of muscle with sarcopenia, and to apply this platform for testing drugs for treatment of sarcopenia. (October 2018)

The goal of this project is to engineer a microchip platform for testing the quality of human multipotent stromal cell growth and differentiation under varying substrate stiffness and extracellular matrix proteins. (September 2018)

Maedeh is a postdoctoral fellow in Dr. Huang's lab.  The aim of her research is to study the effects of extracellular matrix-mediated effects on endothelial-to-mesenchymal transition, with potential applications for improving the efficacy of vascular graft patency.

The AHA Postdoctoral Fellowship is awarded to enhance the integrated research and clinical training of postdoctoral applicants who are not yet independent. The applicant must be embedded in an appropriate research group with the mentorship, support, and relevant scientific guidance of a research sponsor. Recognizing the unique challenges that clinicians, in particular, experience in balancing research and clinical activity, this award mechanism aims to be as flexible as possible to enable applicants to develop academic careers in research alongside fulfilling clinical service commitments. (January 2019)

Karina H. Nakayama is an Assistant Professor in the Department of Biomedical Engineering at Oregon Health & Science University (OHSU). Dr. Nakayama's lab develops regenerative and immunomodulatory biomaterials to enhance engineered vasculature, muscle, and complex multi-tissue composites to develop therapies for ischemic cardiovascular diseases and traumatic musculoskeletal injuries. We approach these engineering challenges using biomaterial spatial patterning and immunomodulation combined with insights gained through computational biology and regenerative rehabilitation. 

Prior to OHSU, Dr. Nakayama received her Ph.D in Biomedical Engineering from the University of California, Davis with her dissertation work aimed at developing regenerative therapies for congenital kidney diseases using decellularized kidney matrices and directed differentiation of stem cells towards renal lineages. She performed her postdoctoral work at Stanford University in the Department of Cardiothoracic Surgery working towards enhancing angiogenesis in ischemic limbs and engineering atheroprotective vascular grafts and myocardial tissues through the manipulation of spatial and mechanical properties.  

This series of studies will develop an engineered therapeutic that is capable of restoring both vascular and muscular function to injured tissues by using spatial cell patterning to enhance the angiogenic potential of vascular endothelial cells. These studies will provide fundamental insights that will inform future regenerative strategies aimed at restoring blood flow to ischemic tissues for the treatment of a broad range of vascular diseases. (January 2018)

Alex is a postdoctoral fellow in Dr. Huang's lab.  The aim of his research is to elucidate the negative effects of chronic nicotine exposure on autologous induced pluripotent stem cells (iPSCs).   He studies the effect of nicotine exposure on endothelial differentiation of iPSCs for therapeutic treatment of peripheral artery disease. Additionally, he develops microchips for optimizing microenvironments for mesechymal stem cells and skeletal muscle myoblasts.

The aim is to evaluate the study the effect of nicotine in the angiogenic capability of induced pluripotent stem cell derived endothelial cells for treatment of peripheral arterial disease. (August 2019)

The sarcoplasmic reticulum (SR) is a membrane-bound structure found within the cardiac muscle cells. Its main function is to regulate the flow of calcium, releasing calcium ions to the surrounding muscle fibers during contraction of the heart muscle and absorbing calcium during relaxation; calcium makes the heart pump. A crucial protein that regulates the function of the SR is phospholamban (PLN); mutations in the PLN gene result in defective PLN which can in turn causes a genetic, or inherited, form of heart failure. The CURE-PLaN network will focus on one particular mutation that is found in patients in the United States and Europe. Their objective is to understand how patients with the mutation develop heart failure, and why not all patients with the mutation have the same clinical course.  Network scientists will use mouse models, and single muscle cell lines to learn more about the genetics of the disease and how to alter the SR and PLN to make heart muscle cells work more efficiently. This Leducq network will work with the PLN Patient Foundation to focus on combatting PLN induced heart failure. Their ultimate goal is to cure PLN induced heart failure in humans.

Dilated cardiomyopathy (DCM) is a leading cause of heart failure. The emergence of induced pluripotent stem cell (iPSC) technology offers an experimental human-based model to predict individual disease manifestations and design targeted therapies. This project advances the concept that patient stem cell derived heart cells can serve as a new paradigm to fill the knowledge gaps in our understanding of how certain gene mutations lead to the DCM phenotype, and ultimately promote the implementation of precision medicine. (June 2018)

The goal of this study is to leverage recent discoveries in human genetics and technological breakthroughs in genome engineering to develop novel therapies for cardiovascular disease. This study will explore the feasibility of using new modalities, such as CRISPR-mediated base-editing, to introduce naturally occurring mutations in the genome that could lower triglyceride levels, potentially conferring cardioprotection. (July 2019)

MicroRNAs (miRNAs) are newly discovered regulators of gene expression in the heart. Karakikes's team will investigate the role of miR-152 in the pathogenesis and progression of diabetic cardiomyopathy. This knowledge should ultimately be of value for understanding the etiology of the disease and they will define potential therapeutic targets for the future treatments. (December 2017)

• AHA Postdoctoral Fellowship

Funding Years: 2019-2020

Awarded for "Deciphering Genotype-Phenotype Association in Hypertrophic Cardiomyopathy”

Hypertrophic cardiomyopathy (HCM) is amongst the most common inherited cardiac diseases, often leading to sudden cardiac death, and heart failure. Current treatments only improve symptoms without addressing the underlying disease cause, while cardiac transplantation remains the only available therapy. Numerous mutations, predominantly in sarcomeric genes, have been implicated in HCM. Inheritance of HCM causing mutations occurs in either an autosomal dominant or in a sporadic pattern. Whole-exome sequencing identified HCM-causing mutations in the thin filament protein Tropomyosin 1 (TPM-1). My preliminary data show that patient-derived TPM-1 induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) recapitulate the HCM clinical phenotype as they exhibit delayed afterdepolarizations (DADs) and triggered activity. Until now there is no available iPSC-CM disease model for TPM-1 induced HCM. In Specific Aim 1, I propose to use iPSC-CM, derived from HCM patients carrying different TPM-1 mutations and healthy controls, to create an ex vivo platform for the study of this form of cardiomyopathy. Furthermore, to obtain novel pathogenetic insights into the molecular processes and signaling pathways of TPM-1 induced hypertrophy, I will perform comprehensive and multi-disciplinary functional assays (Ca imaging, atomic force microscopy, multi-electrode array, and patch clamping among other) as well as transcriptomic analysis (RNA-seq) of single cell TPM-1 iPSC-CM. In addition, the anti-arrhythmic effects of various drugs will also be examined in TPM-1 iPSC-CM. In Specific Aim 2, to reiterate the observed HCM clinical phenotype, I will generate isogenic iPSC lines containing TPM-1 mutations, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. Single cell isogenic iPSC-CM will be subjected to comprehensive functional and transcriptomic characterization to further investigate the pathologic phenotype in the absence of genetic variability. Isogenic patient-derived iPSC-CM will enable future studies towards the identification of therapeutic agents for hypertrophy without the need for patient recruitment. Overall, the proposed studies aim to generate a novel platform for disease modeling and therapeutic applications for TPM-1 induced cardiomyopathy. State-of-the-art methodologies will be used to answer previously intractable questions, elucidate the molecular mechanisms of HCM, and potentially lead to novel therapeutic targets.

Jennifer is a Research Scientist expert in the field of Cardio-Immunology, focusing on developing novel assays to unravel the interactions between inflammatory pathways and cardiovascular diseases (such as heart failure, pulmonary hypertension and cardiovascular aging).

• AHA Postdoctoral Fellowship

Funding Years: 2020–2021

Awarded for "Modulating genome architecture to understand the pathogenesis of Dilated Cardiomyopathy"

LMNA is one of the most frequently mutated genes in dilated cardiomyopathy (DCM). LMNA-related DCM is an incurable disease characterized by cardiac arrhythmias and sudden cardiac death. How mutations in LMNA lead to DCM is poorly understood, translating to the lack of disease-specific therapies. Our overarching goal is to uncover how LMNA mutations induce DCM and thereby develop new tailored therapies for LMNA-related DCM through leveraging new technologies. The LMNA gene encodes A-type lamin proteins, a major component of the inner nuclear lamina. Lamin A plays a critical role in nuclear function via interactions with chromatin at specific regions called lamina-associated domains (LADs). Recently, we have successfully modeled LMNA-related DCM using induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) and shown that lamin A mutations disrupted LAD integrity and dysregulated critical signaling pathways that govern calcium homeostasis and cardiac rhythm. Preliminary data implicated a dysregulation of the PRRX1 gene downstream of disrupted LADs. Based on these findings, we propose the central hypothesis that a LMNA mutation impairs specific LADs and destabilize the chromatin organization, resulting in aberrant expression of genes critical to cardiac physiology. In this project, we aim to delineate the role of chromatin architecture in LMNA-related DCM. We will also develop a novel strategy to modulate the local genome organization. We will utilize a new CRISPR-mediated technology (CLOuD9) to selectively modify the PRRX1 locus and restore the endogenous genome organization to the healthy state. In summary, by combining new technologies, including patient-specific iPSC models of LMNA-related DCM, genomics, epigenomics, and high-throughput functional assays, our study will provide an unprecedented understanding of the relationship between alteration of chromatin architecture and DCM, paving the way for the development of novel mechanism-based therapeutics.

Yuan she completed a major in Biology with Honors and Distinction and a minor in Medical Anthropology at Stanford University (2017). Currently she is a M.D. candidate at Stanford Medicine. She aspires to pursue a career as a physician-scientist in cardiology and cardiovascular sciences.

Award Year: June 2019

Since 1980, the Stanford Medical Scholars Research Program has supported medical student research, both locally and off-site. Students carry out research in an academic setting under the direction of faculty members here at the medical school, hospital and clinics, and throughout the University. The fellowships provide funding and units as Medical Scholars Research 370.