SPUR 2022 Projects: Medicine

Internal Medicine | School of Medicine


CENTRAL MECHANISMS OF HYPOGLYCEMIA DETECTION

Owen Chan, Associate Professor

Hypoglycemia (low blood sugar) is the most serious acute complication in insulin-treated diabetes and it remains the limiting factor in maintaining proper glycemic control. The brain, and especially the ventromedial hypothalamus (VMH), plays a crucial role in sensing hypoglycemia and initiating the physiological hormone responses to correct it. However, both recurring exposure to hypoglycemia and longstanding diabetes can impair the mechanisms that normally correct the fall in blood glucose levels. Our laboratory utilizes a combination of neuroscience (microdialysis, microinjection, optogenetics), metabolic (glucose clamps), genetic (targeted knockdown or overexpression), molecular biology (qRT-PCR, westerns, immunohistochemistry), and cell culture techniques to identify the neural mechanisms that are involved in the detection of hypoglycemia and understand how these central sensing mechanisms are impaired by recurring exposure to hypoglycemia and in diabetes.

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Pediatrics | School of Medicine


HEALTHY HOMES—ASSESSING AND IMPROVING INDOOR AIR QUALITY

Scott Collingwood, Research Assistant Professor

I have been involved in exposure assessment and specifically, environmental influences on the development of health and disease among families for more than a decade. I have ongoing projects where we utilize a variety of air quality monitoring platforms to assess indoor and outdoor air quality at the dwelling unit(home) level of families. Primary pollutants of interest are Particulate Matter of 2.5 micrometers (PM2.5) and Radon. We’re currently adding ozone sensors to the suite of monitoring capabilities we offer. The end goal of my research activities is to relate environmental influences to health and disease—identifying any protective factors that may be present and certainly increasing our understanding of the contributions that pollutants and exposures have on the development of adverse health outcomes. Specifically, the student will contribute to an air quality evaluation of a Healthy Homes intervention program administered by Salt Lake County. This will involve the coordination of activities to obtain outdoor and indoor air quality measurements for a period of at least two weeks prior to the program’s interventions (aimed at improving the air quality in the home) and a post-intervention assessment. The evaluation will capture PM2.5 measures just outside the home, in the most used room of the home, and the primary participant’s bedroom. At the same time, Radon will be measured in the home per standard assessment protocol. Participants in the program are socioeconomically challenged community members with a health malady that may benefit from an improvement in air quality and other home-derived environmental exposures.

NOTE: This project is funded by a grant from the National Institute of Environmental Health Sciences (PIs: Sara Grineski and Tim Collins). In addition to being part of SPUR, it is also part of the HAPPIEST program. Applicants must be University of Utah students who identify in one or more of the following ways (defined by the National Institutes of Health): Blacks or African Americans, Hispanics or Latinxs, American Indians or Alaska Natives, Native Hawaiians, and other Pacific Islanders. Two students will be selected to work on this project together.

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Biochemistry | School of Medicine


LIPID METABOLIC REPROGRAMMING DRIVES LIVER CANCER

Gregory Ducker, Assistant Professor

The transformation of a normal cell into a cancerous one necessitates a profound remodeling of cellular metabolism to support the proliferative phenotype. In perhaps no other tumor type is this change as all-encompassing as in hepatocellular carcinoma (HCC), wherein a very metabolically complex hepatocyte must transition its function away from supporting whole-body metabolism and towards tumorigenic growth. Changes in lipid metabolism are well documented in the development of steatohepatitis that precedes HCC, but whether and how altered lipid metabolism directly contributes to HCC remains unknown. In this project we are working in a zebrafish model to study changes in lipid metabolism that occur upon the transition from a normal cell to a cancerous one. Studying lipid metabolism in cancer is difficult and to address the important questions of not just what is different but how and why they are different, new tools and methods are needed. To address this challenge, our lab is developing new analytical methods to quantify not just steady-state levels of lipids, but also integrate isotope tracing to understand lipid metabolic fluxes. This project will utilize state-of-the-art mass spectrometry tools and is ideal for a student with a strong chemical and analytical background with a deep interest in cancer biology.

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Biomedical informatics | school of medicine


EXPLORING THE EXPOSOME FOR HEALTH RESEARCH

Ramkiran Gouripeddi, Assistant Professor

About 50 – 70% of health and well-being is determined by the environment an individual lives in and their behaviors within these environments. The sum total of all the environmental exposures an individual encounters in their life-time is called the exposome. The exposome includes molecular constituents involved in direct biological pathway alterations as well as mutagenic and epigenetic mechanisms of environmental influences on the phenome. Exposures to different chemicals have been shown to play a role in different conditions including asthma, obesity, as well as other respiratory, cardiovascular, endocrine, and metabolic conditions and cancers. Understanding the effects of these chemical exposures requires representing these molecules in research studies that involve generating and utilizing exposomes. The Center for Exposure Health Informatics Ecosystem (CEEHI) is developing systematic informatics methods for generating and utilizing such exposomes for performing translational research.

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Psychiatry| School of Medicine


EMOTION REGULATION IN DEPRESSION AND THE AGING BRAIN

Joseph Kim, Assistant Professor

Using strategies to control emotions serves as a critical basis for effective social interactions and decision-making. Most of what we know about emotion regulation (ER) come from studies of young adults. However, we cannot assume what we know about younger adults apply to older adults, as there are differences in how the brain functions as we age. Data suggest that these age-related differences become particularly apparent among individuals with a long history of depression. In order to develop effective interventions for older adults, it is critical to study both the brain and behavioral bases of ER in the context of aging. We will study individuals with no history of depression symptoms, in addition to aging adults with lifetime history of depression that present with a range of current depression symptom severity (from mild to moderate). Because intact executive functioning (EF) is a critical component to successful ER, and because EF is known to decline with aging, we will also investigate EF skills and their brain bases as a variable that could impact ER.

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Pediatrics | School of Medicine


THE IMPACT OF AIR POLLUTION ON CANCER SURVIVORS

Anne Kirchhoff, Associate Professor

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Over the past several decades, advancements in the treatment of cancer have led to over 18 million cancer survivors in the United States. While these treatments have greatly extended the life of individuals with cancer, certain cancer therapies can cause heart and lung problems during cancer treatment and lead to chronic conditions that can last throughout a survivor’s life. Particulate matter air pollution (PM2.5) also causes heart and lung morbidity and mortality. Several studies have shown that higher community levels of PM2.5 increases the risk of cancer-related mortality. How PM2.5 air pollution affects the health of cancer survivors and leads to higher morbidity and mortality, however, is unknown. The goal of this research is to determine if exposure to PM2.5 increases the risk of heart and lung health events among cancer survivors, particularly those given treatment regimens with known toxicity.

NOTE: This project is funded by a grant from the National Institute of Environmental Health Sciences (PIs: Sara Grineski and Tim Collins). In addition to being part of SPUR, it is also part of the HAPPIEST program. Applicants must be University of Utah students who identify in one or more of the following ways (defined by the National Institutes of Health): Blacks or African Americans, Hispanics or Latinxs, American Indians or Alaska Natives, Native Hawaiians, and other Pacific Islanders. Two students will be selected to work on this project together.

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Orthopaedics | School of Medicine


ROBOTIC SIMULATOR FOR REPLICATING FOOT AND ANKLE KINEMATICS AND KINETICS

Amy Lenz, Research Instructor

In vitro biomechanics experiments are often 1D/2D tests at non-physiologic speeds, which does not recreate in vivo loads, and in silico models rely on soft tissue and joint contact assumptions. This severely limits translation of laboratory findings into clinical practice. Robotic systems can recreate 3D human motion using cadavers to test pathology, surgical interventions, and implant designs under physiologically relevant conditions. The objective of this project is to contribute to the development of a high-speed robotic foot and ankle simulator driven with subject-specific in vivo kinematics, integrated muscle actuators, and ground reaction force feedback. Experiments on ankle fusion procedures will be a test case for future exploration of other surgeries and simulators to inform clinical care.

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Psychiatry | School of Medicine


NEUROBIOLOGY OF PSYCHIATRIC SYMPTOMS

Erin McGlade, Research Associate Professor

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The Diagnostic Neuroimaging Lab is focused on improving understanding of the neurobiology of psychiatric symptoms, including aggression, suicide behaviors, depression, and anxiety. We use magnetic resonance imaging (MRI) to examine brain volume and connectivity of neural networks in individuals with and without psychiatric disorders. While our lab has numerous studies that the SPUR student would be exposed to, we would focus their efforts on two primary projects looking at aggression and suicide behavior in adolescents and adults. The rationale for these studies is based on data suggesting that rates of females dying by suicide are increasing over time, especially in female veterans. Prior research has identified numerous risk factors for suicide behavior but limited research has focused on females. We therefore examine suicide behavior in females and focus on specific subtypes of aggression (e.g., verbal, physical) as they relate to different brain regions and self-directed violence. Project 1 is a longitudinal study following youth and adolescent participants between the ages of 9 and 19 whereas Project 2 includes female veteran participants. Both projects include data collection and analysis of brain neuroimaging; aggression; suicide and self-directed violence behaviors; neurocognitive constructs such as attention and memory; physical health; mental health; and demographics. Identifying symptom and neurobiological correlates of suicide behavior in females compared to males will enable us to identify early predictors of self-directed violence and co-morbid psychiatric symptoms to improve both earlier intervention and treatment.

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Family & Preventative Medicine | School of Medicine


IMPACTS OF AMBIENT AIR POLLUTION ON PRE-TERM BIRTH AND ASSOCIATED HEALTHCARE COSTS

James VanDerslice, Professor

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Exposure to ambient and indoor air pollution, particularly PM2.5, has been associated with multiple adverse birth outcomes including pre-term birth (PTB), defined as birth with a gestational age of less than 37 weeks, (Ghosh,et al., 2021; Stieb et al., 2012) and these effects may depend on the timing of exposure during gestation (Chen et al., 2021). Personal, home and community factors may change the relationship between ambient PM2.5 exposure and the risk of pre-term birth (Lu, et al., 2021; do Nascimento et al., 2022). However, it is difficult to disentangle the household and parental factors from intrinsic genetic factors that affect fetal growth. Further, impacting policy often requires arguments based on cost and the cost of pre-tem birth is significant (Waitzman, Jalali, & Grosse, 2021). While better estimates of the associations of exposure specific risks and timing is critical, so is information on the costs resulting from the adverse health effects caused by exposure to air pollution.
The Specific Aims for this project are:

1. Estimate the association between trimester-specific exposure to PM2.5 and near-road exposures and the risk of PTB in Utah.
2. Estimate the healthcare-related costs associated with the excess number of PTB in Utah.

Daily air quality predictions at a 1km2 resolution will be linked to pregnant women throughout pregnancy and used to assess the relationship between trimester specific exposures and the risk of PTB.

NOTE: This project is funded by a grant from the National Institute of Environmental Health Sciences (PIs: Sara Grineski and Tim Collins). In addition to being part of SPUR, it is also part of the HAPPIEST program. Applicants must be University of Utah students who identify in one or more of the following ways (defined by the National Institutes of Health): Blacks or African Americans, Hispanics or Latinxs, American Indians or Alaska Natives, Native Hawaiians, and other Pacific Islanders. Two students will be selected to work on this project together.

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