May 17, 2023

DOM INVESTIGATOR: From Bench to Bedside

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Researcher Spotlight

May Researcher Spotlight: Milka Koupenova

In this month’s Researcher Spotlight, we highlight the work of Milka Koupenova, PhD, assistant professor of medicine in the Division of Cardiovascular Medicine.  


Dr. Koupenova’s research focuses on understanding the molecular mechanisms that underline platelet-mediated immune response during viral infections and how this response contributes to cardiovascular disease. Specifically, she is currently interested in SARS-CoV-2- or influenza-mediated sensing and signaling in platelets that may lead to an increased risk of thrombosis and coagulation. The long-term goal of her lab is to characterize the molecular sensors and signaling in platelets mediated by viruses with different genomes, and identify how these viruses may lead to non-classical platelet activation, platelet “death”, and consequently, to the impact on the surrounding environment. She is currently the principal investigator on an NIH-funded R01, "Mechanisms of Platelet Reprogramming During Influenza Infection," where she is examining the role of a previously undescribed molecular mechanism in platelets that leads to the sensing of influenza and ultimately increased thrombosis. Dr. Koupenova is also the principal investigator on an internally funded CTSA project, “The Role of Platelets and Leukocytes in COVID-19 Associated Thrombotic Risk,where she is studying the platelet-mediated leukocyte response during SARS-CoV-2 infection. As part of Dr. Koupenova’s contributions to understanding the impact of COVID-19 on cardiovascular disease (CVD) she has organized and co-edited a compendium of ten articles on COVID-19 and CVD for the American Heart Association journal Circulation Research that is coming out this month. 


Dr. Koupenova cares deeply about scientific rigor, creativity, productivity, and diversity in her lab, in academic research, and in medicine. Of this she says, “Our lab believes that the future of scientific discovery rests in the hands of creative minds and productive collaborations between scientists from diverse backgrounds and cultures. We welcome anyone with a passion and love for science and improving health disparities.” Indeed she is committed to supporting the growth of a diverse team of researchers here at UMass Chan and in the Department of Medicine, having served in various capacities for the Cluster Hire Initiative. Through this initiative, she was a reviewer of the UMass Chan Cluster Hire Diversity Statement and reviewed applications for the divisions of Infectious Diseases and Immunology, and Innate Immunity. She has also served on the Diversity in Research Taskforce and was a co-representative for UMass Chan at the Annual Biomedical Researcher Conference for Minority Students.  


Dr. Koupenova earned her PhD in Biochemistry from Boston University School of Medicine in Boston, Massachusetts. Following her PhD studies, she completed postdoctoral training in Platelet Biology and Thrombosis at the Whitaker Cardiovascular Institute at Boston University School of Medicine under the mentorship of Drs. Jane Freedman and Katya Ravid, and Platelet Immunology at UMass Chan Medical School, under the mentorship of Dr. Freedman. Dr. Koupenova started her independent lab at UMass Chan in 2020 and continues to explore the contribution of the immune related sensors in platelets to thrombosis. 

 

We are grateful for Dr. Koupenova’s contributions and commitment to the mission and core values of the Department of Medicine.  


Learn more about Dr. Koupenova by clicking the button below.

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Trainee Spotlights

Left to Right: Liraz Galia, Kevin Gao, and Samantha Tse

In this month’s Trainee Spotlight, we feature Liraz Galia, PhD, postdoctoral fellow in the lab of Kate Fitzgerald, PhD, professor of medicine, associate vice provost for basic science research, vice chair for research in the Department of Medicine, chief of the Division of Innate Immunity and director of the Program in Innate Immunity, Samantha Tse, MD/PhD student in the lab of Read Pukkila-Worley, MD, associate professor of medicine in the Division of Infectious Diseases and Immunology, and Kevin Gao, MD/PhD student in the labs of Dr. Fitzgerald and Ann Marshak-Rothstein, PhD, professor of medicine in the Division of Rheumatology. They were the recipients of the inaugural RISE: The Robert W. Finberg, MD Memorial Research Training Awards and presented their research at Innate Immunity Day 2023: Mechanisms and Methods of Cell Death on Wednesday, May 10. 

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Liraz Shmuel-Galia, PhD, is a postdoctoral fellow at UMass Chan Medical School, who is originally from Beer Yaacov, a small town in Israel. This summer, Dr. Galia will complete her postdoctoral work at UMass Chan and start her own lab at UT Southwestern. We wish her all the best in her future endeavors! 

 

What is your research focus? 

My research is focused on exploring novel regulatory mechanisms that control innate immune responses in the intestinal tract. While working in Dr. Fitzgerald’s lab, I began studying long noncoding RNAs (lncRNAs) and their role in the regulation of innate immunity. With a strong background in mucosal immunology, my goal was to address the lack of understanding about lncRNAs in intestinal inflammation. I identified a highly conserved lncRNA, HOXA11os, as a key regulator of intestinal homeostasis and found a previously unreported transcript of HOXA11os that is transcribed in the nucleus and translocated to the mitochondria in cells of the distal colon (Shmuel-Galia et al., submitted). This study uncovered a new metabolic signaling pathway that bridges mitochondrial metabolism and the onset of colitis through expression of the lncRNA, HOXA11os, and provides the first characterization of how a lncRNA regulates mitochondrial metabolic function at a tissue level and how its dysregulation can impact disease outcome. 

 

In my independent lab at UT Southwestern, I will investigate how innate immune signaling regulates intestinal inflammation and homeostasis. I envision developing a research program that utilizes novel approaches to study the precise molecular and cellular mechanisms by which proteins, as well as lncRNAs, regulate immune responses in the gut. 

 

Why did you choose UMass for your postdoctoral studies? 

I chose UMass for my postdoc because of its reputation for conducting high-quality research in my field of interest. I was drawn to the collaborative and supportive environment that fosters scientific innovation. Furthermore, as someone from Israel, I was excited at the prospect of experiencing a new environment and climate, particularly the opportunity to explore snow and the beautiful New England scenery. Finally, I was thrilled at the opportunity to work with my PI, Dr. Fitzgerald, whose work I have long admired. 

 

Where is your favorite place to travel for vacation and why? 

I enjoy going to tropical destinations, where I can experience the warm weather and partake in activities such as diving. I find it fascinating to explore new cultures and traditions, which is always an exciting aspect of my travels.  

 

What is your favorite game or sport to watch and play? 

I enjoy playing Newcomb ball with my friends, it’s a fun way to stay active and socialized. Recently, my young son started playing soccer and I have grown to love both watching and playing the game with him.  

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Samantha Tse, is an MD/PhD student at UMass Chan Medical School, who is originally from Belmont, Massachusetts.  

 

What are your research and clinical interests?  

I am interested in uncovering mechanisms of pathogen detection in the host intestine, particularly in the nematode Caenorhabditis elegans (C. elegans), and the regulation of intestinal innate immunity. I aspire to practice gastroenterology as a physician-scientist studying host defenses in the developing intestine.  

 

What makes UMass a great place for your studies?  

UMass is home to some of the greatest minds in the field of C. elegans and is a hub for innate immune research. 

 

Favorite hobby?  

Too many! I love to paint, draw, meditate, and take long walks in the park with my puppy, Luna.  

 

Favorite thing to do in Worcester/Worcester area?  

Exploring the many hole-in-the-wall restaurants.    


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Kevin MingJie Gao, is an MD/PhD student at UMass Chan Medical School, who is originally from Radnor, Pennsylvania. 

 

What are your research and clinical interests? 

My research interest is centered around understanding immunologic diseases, which harm one’s own body, especially in the context of autoimmunity and autoinflammation. During my PhD work, I primarily utilized mouse models to study how immune activation by the cytosolic DNA sensing pathway cGAS-STING can promote inflammatory disease within the lung. Next in my training as a physician-scientist, I am seeking to apply my basic immunology training towards understanding and treating dysregulated immunologic processes in patients suffering from rheumatologic and immune disorders. I am interested in clinically specializing in either rheumatology or allergy-immunology.  

 

What makes UMass a great place for your studies? 

The culture of camaraderie, collaboration, and support within the UMass community has been so critical to my growth as an independent thinker. Our fellow researchers at all levels of training contribute constructive feedback and insightful discussion that is the backbone of research efforts within our institution.  

 

Favorite hobby? 

Besides my love of medicine and immunology, I am also very passionate about learning tricks with juggling clubs and other related circus props and skill toys like meteor hammers and kendama. 

 

Favorite thing to do in Worcester/Worcester area? 

Spending time at the New England Botanical Gardens at Tower Hill is always lovely. Annual memberships are significantly discounted for students, and you can also get a membership for your dog to explore their various outdoor gardens and trails.  

In the News

Innate Immunity Day 2023

Innate Immunity Day 2023: Mechanisms and Methods of Cell Death was held on May 10, 2023, in the Albert Sherman Auditorium. The Program in Innate Immunity thanks all the speakers, RISE awardees, participants, and program chairs for an exceptional day of scientific talks and great conversation over coffee and cookies during the break.


Related: Inaugural Finberg Memorial Award winners to present at Innate Immunity Day

Honghuang Lin Leads Study Using AI to Identify Signs of Early Cognitive Decline 



Honghuang Lin, PhD, FAHA, professor of medicine in the Division of Health Systems Science and a director in the Program in Digital Medicine, recently spoke with the Telegram & Gazette about a study he is leading that uses artificial intelligence (AI) to identify early signs of cognitive decline that could be linked to dementia and Alzheimer’s disease. The study is a partnership between UMass Chan Medical School and Linus Health, with the aim that early detection of cognitive decline can prompt faster treatment, potentially slowing down the disease’s progression.


Using a clock-drawing test, patients are asked to draw a clock on an iPad, rather than using pen and paper. “A traditional test might miss subtle imperfections in the lines drawn or placement of numbers in the clock. AI not only captures that information but also pools the results from all study participants to identify trends that could unlock patterns in early cognitive decline,” Dr. Lin explained to the T&G. 


Additionally, the study team asks patients to recall three words at the end of the exam, take a 32-question lifestyle survey, and receive a brain health action plan based on their responses. The answers to the questions are then used to recommend various lifestyle changes that can improve brain health. Dr. Lin explains that using the AI exam is much faster than traditional exams, with results within minutes. The immediate results can then be used to develop action and care plans for patients. 


Jeevarathna Subramanian, MD, associate professor of medicine and a primary care physician in the Division of General Internal Medicine commented, “The goal is to potentially introduce the AI test into primary care practices worldwide.” The study team hopes to test 150 patients through this summer and that this work will lead to a broader clinical trial to further test this AI technology in the future. 

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Recent Publications

CHORDS Team Led by Hong Yu Link Social Determinants of Health and Suicide Risk in Recent Study 



Hong Yu, PhD, adjunct professor in the Division of Cardiovascular Medicine, and the director of the Center of Biomedical and Health Research in Data Sciences (CHORDS) at UMass Lowell, recently led a study, “Associations Between Natural Language Processing–Enriched Social Determinants of Health and Suicide Death Among US Veterans,” that was published in JAMA Network Open. Here, investigators studied the link between suicide risk among veterans and social determinants of health (SDOH), such as housing instability, financial problems, and violence. The findings revealed how natural language processing (NLP), a form of artificial intelligence, can be used to analyze available information about social determinants of health, which leads to better suicide risk assessment and prevention. 

 

The study team developed an NLP that could extract SDOH from unstructured clinical notes in the U.S. Veterans Health Administration’s electronic health records, a first of its kind study at a large scale. Using the data, researchers were able to better identify patients at risk of suicide based on their social determinants of health and providers could then share appropriate resources with patients. Although this study was conducted with veterans, it is expected that the results would translate to the general population as well.  

 

About CHORDS 

The UMass Lowell Center of Biomedical and Health Research in Data Sciences (CHORDS) conducts cutting-edge informatics research to accelerate biomedical and healthcare discoveries through innovative computational methods and technologies in information science, data science and translational science. David McManus, MD, the Richard M. Haidack Professor in Medicine and chair of the Department of Medicine, serves as a co-director of CHORDS. 

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Vandana Nagpal, Jennifer Reidy, and Colleagues Study Feasibility of Palliative Care Intervention for Patients with Catastrophic Stroke  

Vandana Nagpal, MD, associate professor of medicine and associate chief, and Jennifer Reidy, MD, the Joy McCann Professor for Women in Medicine, associate professor of medicine and chief – both in the Division of Palliative Care Medicine, along with colleagues from Neurology, recently had their study, “Improving Access to Specialist Palliative Care for Patients with Catastrophic Strokes Using Best Practice Advisory – a Feasibility Study,” published in The Neurohospitalist.  

 

Stroke is one of the leading causes of death and long-term disability in the United States but palliative care utilization in stroke is low compared to other diseases such as cancer, heart failure, and liver and renal disease. Palliative care is recommended by the American Heart Association and American Stroke Association to help patients and families navigating life-altering stroke, but studies have shown that only a small fraction of patients receive palliative care consultation. 

 

In this quality improvement project, the study team developed a Best Practice Advisory (BPA) that was delivered through Epic, for patients with a National Institutes of Health Stroke Scale (NIHSS) score of greater/equal to 20 (patients with higher scores are less likely to recover and are considered critically ill). The BPA served as a reminder to the primary stroke team to consider a goals-of-care discussion and consultation with the palliative care service for these patients and prompted a needs assessment for the whole interdisciplinary team. The goal of this project was to study how the BPA was intervened upon by care teams and whether it increased palliative care consultations in stroke patients. 

 

Results showed the BPA triggered accurately in Epic for all patients with an NIHSS score greater than/equal to 20 and palliative care consultations resulting from the BPA increased from the first year of implementation to the next two years. More work needs to be done to refine the parameters of how the BPA is triggered but ultimately, this intervention could be an important way to address unmet needs of stroke patients and their families in the neurocritical care setting. 

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New Review from the Trivedi Lab Describes the Lymphatic System in Organ Development, Function, and Regeneration” 

 

Chinmay Trivedi, MD, PhD, professor of medicine in the Division of Cardiovascular Medicine, Harish Janardhan, MD, PhD, a postdoctoral fellow in the Trivedi lab, and Roy Jung, a PhD student in the Trivedi lab, recently had their work published in Circulation Research.


Their review titled Lymphatic System in Organ Development, Function, and Regeneration focuses on the functionality and importance of the lymphatic systems in the body’s immune defense against pathogens, fluid homeostasis in the extracellular regions, transport of nutrients and signaling molecules to the blood, and tissue growth.  

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News from the Clinical Research Core

Reminder: Fundamentals of Clinical Research - Mini Course

The DoM Clinical Research Core would like to remind the research community that the Fundamentals of Clinical Research - Mini Course, presented by Bruce Barton, PhD, Robert Goldberg, PhD, and Heather Strom Tessier, MS, is being held Mondays and Wednesdays throughout May and June of 2023.


This lecture series is designed for students in training, residents, post-doctoral fellows, and junior faculty who are interested in learning about the most commonly employed study designs used in clinical and public health research and about the IRB review process.


Learn more by clicking the button below.

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Funding Opportunities and Notices