NUCATS Awards Four Pilot Grants
The Northwestern University Clinical and Translational Sciences (NUCATS) Institute has announced pilot grant funding to four Northwestern research teams. The awards followed a robust pool of studies that included more than 50 applications. The funded projects will explore the effects of genetic mutations on human skin disorders; cardiovascular diseases among second-generation South Asian Americans; the effects of social determinants of health on cardiovascular disease; and underrepresented group participation in Parkinson’s disease research.
“The continuation of advances against disease is critically dependent on the ingenuity and determination of faculty just starting their careers in translational research,” says Richard D’Aquila, MD, director of the Northwestern University Clinical and Translational Sciences (NUCATS) Institute, the Howard Taylor Ricketts, MD, Professor of Medicine, and associate vice president of Research. “NUCATS Pilot Awards, as well as the Dixon Translational Research Grants and the Giddan Awards that we help administer, are competitions for seed funding to test the most promising new ideas, thereby enabling an NIH grant application in the near future that can launch a career that will impact the health and well-being of uncounted lives for many years to come.
“I want to emphasize how grateful we are for the generosity of our partners at the Dixon and Giddan Foundations, who share our vision of advancing discoveries to improve health, and the very many outstanding applicants in this cycle. It gives me confidence that advances in health for all will indeed keep accelerating.”
Priority areas for this round of pilot funding included projects with a high likelihood of translation to clinical or population health impact, projects that align with the Chicago Department of Public Health's Healthy Chicago 2.0/Healthy Chicago 2025 goals, and studies that address health disparities/health equity.
Exploring Genomic (Intronic) Mutations and Skin Disease
“Human Skin Disorders Modulated by ALOXE3 Intronic Polyadenylation,” a study led by Xiaomin Bao, PhD, Molecular Biosciences and Dermatology, seeks to determine how the gene ALOXE3 is controlled by the non-coding regions of the genome. ALOXE3 is associated with multiple rare skin disorders. The ALOXE3 mutations that cause these disorders are not all mapped to protein-coding regions, which suggests that there may instead be mutations in the non-coding genomic regions.
“The ultimate goal is to decipher how these ‘junk’ sequences of the human genome could influence disease inheritance and progression,” explains Bao. “Human genes are comprised of both exons (protein coding) and introns (non-coding). The intronic regions are conventionally considered junk because these sequences are removed before RNA is used as templates for protein synthesis. However, we recently discovered hundreds of ‘stop signals’ in the introns frequently used by skin epidermal cells. These stop signals impair full-length gene function. One of these stop signals is located in an intron of ALOXE3.
The research team will attempt to determine how genetic elements in the introns contribute to the development of skin diseases.
“With future support, we would love to keep exploring the fundamental mechanisms underlying the recognition and usage of specific ‘stop signals’ in the introns, in both normal and diseased skin cells. There are hundreds of these sites across the human genome, and we are just beginning to understand this,” says Bao.
How Are Race and Ethnicity Related to Propensity for Heart Disease?
Heart disease is the most common cause of death in the United States, and two new pilot grants will focus on cardiovascular illness. Both studies aim to show the importance of cardiovascular disease prevention starting at an early age.
The aptly named “Multi-level Assessment of the South Asian Life-course of Atherosclerosis (2nd Generation Offspring Study),” or MASALA-2G, led by Feinberg instructor of Medicine in the Division of Cardiology and Preventive Medicine Nilay Shah, MD, MPH, seeks to identify the contributors to cardiovascular health among second-generation South Asian Americans.
“We know that the South Asian American community has a disproportionately higher burden of cardiovascular disease compared to other racial and ethnic groups,” says Shah, who stresses the significance of figuring out how to preserve and maintain cardiovascular health early in life, even before risk factors develop.
The goal of the MASALA-2G study is to gain an understanding of what contributes to declines in cardiovascular health in the younger second-generation South Asian American population in order to design, target, and implement interventions to prevent cardiovascular disease from an early age.
Along with his passion for cardiology, Shah has personal ties to the study. “I am most excited that this research will be relevant not only for the patients I see, but also for the community in which I grew up. In cardiology we tend to see patients of South Asian background experiencing a cardiovascular disease event like a heart attack at surprisingly young ages, sometimes as young as their 30s.” One goal of this research will be to limit these occurrences.
Poverty Hurts Hearts
Amanda Marma Perak, MD, MS, principal investigator for “Microbiomic Mechanisms of Associations Between Early-Life Social Determinants of Health and Subclinical Cardiovascular Disease Phenotypes,” has similar empathy for vulnerable populations. This study, which seeks to determine the effect of social determinants of health on the human microbiome, and thus, on cardiovascular health, finds its basis in patients’ social status instead of in their ethnic background.
“Individuals with adverse social circumstances in childhood have higher rates of cardiovascular diseases in adulthood,” says Perak. Some of these adverse social circumstances, such as a lack of access to healthy foods and safe spaces for exercise and sleep, have obvious effects on health. Other factors, such as environmental toxins (like pollution) and stress (from exposure to violence and racism, for example), are less well understood.
To explore how exactly these circumstances negatively affect heart health, and thus how best to prevent cardiovascular disease, Perak, along with co-investigators Donald Lloyd-Jones, MD, ScM, and Patrick Seed, MD, PhD, plans to collect stool samples from young adults who have already been studied extensively in the Fragile Families and Child Well-Being Study. These samples will allow researchers to examine the potential role of the gut microbiome — the healthy bacteria that normally live in our bodies — in responding to adverse social conditions by causing blood vessel and heart changes that lead to cardiovascular disease.
“We need to come up with ways to interrupt the path from social adversity to physical disease. If we find that the gut microbiome has an important role, this could open up a new field for development of interventions to prevent cardiovascular disease in vulnerable populations,” says Perak.
Like Shah, she is committed to making healthcare access and knowledge more equitable for marginalized populations.
Getting Chicagoans Excited About Parkinson’s Research
The fourth grant, respectively, was awarded to another project seeking to overhaul healthcare disparities. The “Community-academic initiative to measure and improve underrepresented group participation in Parkinson’s disease research,” led by Danielle Larson, MD, focuses on how negative social circumstances affect health, this time through the lens of Parkinson’s disease.
Through the development and expansion of the Chicago Movement Coalition (CMC), a program that partners with academic institutions, community members, and local organizations in Chicago to help narrow the gaps in Parkinson’s disease awareness and access, Larson and her team aim to assess the attitudes of underrepresented groups toward Parkinson’s disease research.
“Parkinson’s disease is the second-most common neurodegenerative disease, but there is still a void in awareness of the disease and access to resources in underserved communities of Chicago,” says co-investigator Jennifer Adrissi. “Although academic and community resources are available, they can be inaccessible due to location or lack of promotion in these underrepresented communities.” This lack of accessibility contributes to disparities in clinical research participation and access to Parkinson’s disease education and care, which can contribute to delayed diagnosis of the disease.
Adrissi recognizes the vitality of relationship-building within communities: “With each workshop and community partnership, we learn more about the communities we serve and build an alliance with the common goal of decreasing the morbidity of people with diagnosed and undiagnosed Parkinson’s disease in our underserved populations.”
Because of the COVID-19 pandemic, Larson, Adrissi, and co-investigators Karen Williams and Emily Zivin have been planning community-based events for a virtual landscape. They plan to equip community leaders with the skills necessary to become “Parkinson’s ambassadors” in their organizations and neighborhoods. Adrissi is thrilled that “As the CMC continues to grow and its impact continues to spread, we chip away at the barriers to access and resources that have led to disproportionate suffering in our underserved communities.”
The team adds that the CMC is always interested in adding to its network of community partners, especially those serving underrepresented communities in the Chicagoland area. Interested community organizations can email or visit the CMC website for more information.
Written by Morgan Frost