Announcements Funding CTRFP Awardees ICTS News

ICTS Announces 2021-2022 CTRFP Awardees

(top, left to right) Beau Ances, MD, PhD, MS; Kevin Black, MD; Michael Durkin, MD, MPH; Manu Goyal, MD, MSCI; Umang Jain, PhD (middle, left to right) Sheng Chih Jin, PhD; Melissa Lewis, PhD; Chieh-Yu Lin, MD, PhD; Kerri Morgan, PhD; Stephen Oh, MD, PhD; Nandini Raghuraman, MD, MS (bottom, left to right) Naresha Saligrama, PhD; Celia Santi Grau Perez, MD, PhD; Rodrigo Vazquez Guillamet, MD; Fei Wan, PhD; Pamela Xaverius, PhD; Jin Zhang, PhD

Washington University Institute of Clinical and Translational Sciences (ICTS) and The Foundation for Barnes-Jewish Hospital awards 17 investigators as part of the 14th annual Clinical and Translational Research Funding Program (CTRFP). The CTRFP is the largest internal grant funding program of the ICTS. Applicants are required to submit proposals for projects that promote the translation of scientific discoveries into improvements in human health. For 2021, awards were considered across three project categories: clinical/translational, community-engaged research, and biostatistics, epidemiology, and research design.

This year the CTRFP received over 80 letters of intent and awarded approximately $725,000 for investigator-initiated projects. These grants are supported with funding from the ICTS, The Foundation for Barnes-Jewish Hospital and our partner institutions: Saint Louis University and the University of Missouri-Columbia.

Funding is made available to the 2021 awardee cohort effective March 1, 2021.

Serum Neurofilament Light (NfL) as a Marker for Brain Injury in Individuals Undergoing Chimeric Antigen Receptor-modified T Therapy

PI: Beau Ances, MD, PhD, MS
Washington University School of Medicine: Neurology

Cellular therapies have revolutionized the treatment of terminal blood cancers like lymphoma. However, they are often associated with severe neurological side-effects, termed immune effector cell-associated neurotoxicity syndrome (ICANS). This study examines the role of neurofilament light chain (NfL) as a potential biomarker for both the development of ICANS and the long-term consequences of ICANS on cognition (memory and attention).

Peripheral Induction of Inhibitory Brain Circuits to Treat Tourette’s: Pilot Study

PI: Kevin Black, MD
Washington University School of Medicine: Psychiatry

In June, 2020, researchers described a new potential treatment for Tourette syndrome (TS). Rhythmic stimulation of a nerve at the wrist induced brain activity at the same frequency in the brain, and reduced tic frequency and severity in 19 TS patients. We will test whether we can replicate this clinical benefit, whether it exceeds any benefit from nonrhythmic stimulation (active placebo), and how long benefit lasts after stimulation ends.

Dissemination and Implementation of an HCV Telehealth Program for PWID

PI: Michael Durkin, MD, MPH
Washington University School of Medicine: Department of Medicine – Infectious Diseases

The opioid epidemic is fueling a surge in hepatitis C virus (HCV) infections. Injection drug use is now the most common cause of HCV infection in the United States. This grant will evaluate facilitators and barriers to a telehealth based HCV treatment model for persons who inject drugs (PWID) and pilot test the impact of an expanded telehealth program on the HCV care cascade among persons who use drugs.

Cerebral Metabolism in Multiple Sclerosis Before and After Disease Modifying Therapy

PI: Manu Goyal, MD, MSCI
Washington University School of Medicine: Radiology – Neuroradiology

This project will collect magnetic resonance and positron emission tomography data to measure the cerebral metabolic rate of oxygen and glucose in patients with multiple sclerosis (MS) before and after initiation of highly efficacious therapy. We will investigate differences in metabolism in the MS brain compared to controls. We will assess if these differences correlate with markers of disease severity and are modified by initiation of therapy.

A Novel Serum Biomarker for Subtyping Inflammatory Bowel Diseases

PI: Umang Jain, PhD
Washington University School of Medicine: Pathology and Immunology

There remains a major unmet need for reliable noninvasive biomarkers that can distinguish between Crohn’s disease and Ulcerative colitis, two principal manifestations of IBD. We have recently identified an overwhelming enrichment of a novel yeast Debaryomyces hansenii in the inflamed lesions of CD and this proposal will investigate if serum antibody titers against D. hansenii can accurately subtype IBD.

Long-Read Genome Sequencing and Integrative Genomic Analysis for Cerebral Palsy

PI: Sheng Chih Jin, PhD
Washington University School of Medicine: Genetics

In addition to commonly associated environmental factors, epidemiological studies suggest genetic factors may cause cerebral palsy (CP). Therefore, we hypothesize that genetic variations may account for a large proportion of CP cases. This project utilizes a well-phenotyped cohort, comprehensive genomic data, and robust statistical methods to identify novel genetic etiologies and biological pathways that contribute to the CP pathogenesis.

Pilot and Evaluation of the Indigenous Health Toolkit

PI:  Melissa Lewis, PhD
University of Missouri-Columbia, School of Medicine: Family and Community Medicine

Building on previous research and community partnerships, this project aims to pilot and evaluate the Indigenous Health Toolkit at two sites. The aim of the toolkit is to improve the knowledge, skills, and beliefs of healthcare providers working with Indigenous patients.

Molecular Imaging of CCR2 to Visualize Active Sarcoidosis

PI:  Chieh-Yu Lin, MD, PhD
Washington University School of Medicine: Pathology and Immunology

Sarcoidosis is an inflammatory disease that affect multiple organs with morbidity and mortality. The involvement of heart can cause up to 85% of deaths in sarcoidosis patients. However, we currently do not have a good tool to accurately diagnose this dire condition, and to monitor patients after treatment. Therefore, we propose to test our FDA-approved specific molecular imaging tracer for diagnosing and monitoring sarcoidosis patients.

Adapting mHealth Technology to Improve Patient Activation and Overall Wellness for Persons with Disabilities

PI:  Kerri Morgan, PhD
Washington University School of Medicine: Occupational Therapy

Persons with disabilities (PwD) commonly experience fatigue, which often negatively impacts their everyday lives. Management of this symptom can be challenging. Satisfaction with current interventions to manage fatigue is low among PwD and there is a desire for more personalized approaches. The purpose of this study is to develop and test a fatigue self-management intervention using mobile phones that is personalized to each person’s needs.

Interrogating the Bone Marrow Microenvironment of Myeloproliferative Neoplasms via Imaging Mass Cytometry

PI:  Stephen Oh, MD, PhD
Washington University School of Medicine: Department of Medicine – Hematology

The goal of this project is to characterize and localize specific cell types in the bone marrow of patients with myeloproliferative neoplasms (MPNs). Utilizing a technology called imaging mass cytometry (IMC), we aim to identify features that define specific MPN subtypes such as essential thrombocythemia and myelofibrosis. We hope to translate these efforts to aid in clinical assessment of MPN patients.

Trends in Oxidative Stress during Labor and Delivery

PI:  Nandini Raghuraman, MD, MS
Washington University School of Medicine: Obstetrics and Gynecology

Supplemental oxygen is commonly administered to laboring mothers in response to the fetal heart rate, despite evidence that over-oxygenation may be harmful due to free radical mediated oxidative cell damage. This project examines baseline trends in oxidative stress in mothers throughout labor and delivery in order to identify high-risk stages of labor when the mother and baby may be most vulnerable to oxidative stress and over-oxygenation.

Immunophenotypic Analysis and Protein Biomarker Study in Pediatric Onset Multiple Sclerosis

PI:  Naresha Saligrama, PhD
Washington University School of Medicine: Neurology

Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS). Pediatric-onset MS (POMS), is defined as MS with onset before the age of 18 years. Up to 10% of MS patients are POMS. Extensive progress has been made in understanding the immunopathogenesis of adult MS; however, there are only a handful of studies addressing these in POMS. In this study, our aim is to characterize immune abnormalities in children with MS.

A New Tool to Monitor Sperm Capacitation and Its Use for the Diagnosis and Treatment of Male Infertility

PI:  Celia Santi Grau Perez, MD, PhD
Washington University School of Medicine: Obstetrics and Gynecology

Fertility specialists have no simple, objective way to decide which fertility treatment to recommend to the 25% of infertile men with normal-looking sperm. Our objective is to validate a simple method specialists can use to determine the ability of the sperm to fertilize the egg. If our assay works, fertility specialists could use it to quickly test a man’s sperm and determine which treatment to recommend to achieve pregnancy.

Quantitative Computed Tomography to Size Match Donors and Recipients

PI: Rodrigo Vazquez Guillamet, MD
Washington University School of Medicine: Department of Medicine – Pulmonary and Critical Care Medicine

Lung transplantation is a lifesaving procedure for people suffering from end-stage lung diseases. Lungs that are too big or too small for the recipient carry the risk of surgical complications. Currently, we can only predict donor’s lung size. Because lung volume predictions are not accurate, size mismatch and its complications continue to occur. We will use of quantitative compute tomography to obtain actual donor lung volumes for first time.

Two-stage Instrumental Variable Parametric and Semi-Parametric Accelerated Failure Time (AFT) Model for Survival Outcome

PI:  Fei Wan, PhD
Washington University School of Medicine: Surgery – Public Health Services

Limitations of randomized studies have led cancer researchers to increasingly design large observational studies. Conventional statistical methods will fail in presence of unmeasured confounding. The commonly used instrumental variable method-2SRI Cox model is also biased and the alternative of 2SRI additive hazards model has limitations. We propose to evaluate the performance of 2SPS and 2SRI parametric and semi-parametric AFT models.

Housing, Families and Well-Being

PI:  Pamela Xaverius, PhD
Saint Louis University, College for Public Health and Social Justice: Epidemiology and Biostatistics

We will evaluate an intervention to be delivered in a public housing complex that is aimed at improving the well-being of pregnant women and families with children under the age of five living in that complex. The intervention will be co-designed by the community it intends to serve, and the evaluation with include authentic community engagement in all aspects of research design, delivery, and dissemination.

Examining Cervical Cancer HPV Genotypic Radiation Response using Augmented Structural Gene Expression Differences

PI:  Jin Zhang, PhD
Washington University School of Medicine: Radiation Oncology

HPV is the primary cause of cervical cancer; however, virus strain specific induction of cancer gene expression is unclear due to paucity of data for all high-risk HPV subtypes. This proposal will develop an advanced machine learning approach that requires only about 10 samples for each virus strain to discover HPV genotypic induction of transcription differences that otherwise would require hundreds or more samples to discover using standard methods.