Published January 20, 2021
The University at Buffalo’s Clinical and Translational Science Institute (CTSI) has awarded 13 new grants to support innovative translational research projects in Western New York. The CTSI Translational Pilot Studies Program provides seed money to investigators to assist them in developing promising new technologies and therapeutics from the conceptual stage to clinical studies.
“The pilot studies grant awardees for 2021-22 include projects that address significant translational research questions,” says CTSI Pilot Studies Program Director Brahm Segal, MD, Chair, Department of Internal Medicine, Chief, Division of Infectious Diseases, and Professor of Oncology, Roswell Park Comprehensive Cancer Center. “In addition to developing new methods and technologies, these projects will foster cross-disciplinary collaborations and mentoring relationships.”
Recipients of 2021-22 Translational Pilot Studies Program awards are:
Principal Investigator: Kafuli Agbemenu, PhD, MPH, RN, CTN-A, School of Nursing
Co-Investigators: Sonya Borrero, MD, MS, Director, Center For Women’s Health Research and Innovation, University of Pittsburgh; Gretchen Ely, PhD, School of Social Work; Helen (Hua) Wang, PhD, Department of Communication, College of Arts and Sciences; Sondra Dawes, BS, Jericho Road Community Health Center — Priscilla Project; Francine Rwanika, Jericho Road Community Health Center — Priscilla Project
Unplanned pregnancy occurs disproportionately among low-income women, women of color, and immigrant women. A particularly marginalized group in the United States is that of African refugee women, a steadily increasing subset of the African immigrant population, with overall poorer reproductive health outcomes due to decreased access to healthcare, language barriers, low socioeconomic status, and potentially lower education levels. Unplanned pregnancy can be mitigated by provision of contraceptive education, a need that has been identified by previous studies in this population. Hence, this study aims to address gaps in the healthcare environment by modifying an existing family planning intervention to be culturally congruent for African refugee women in the Buffalo region. In addition, researchers will conduct feasibility and usability testing of the developed culturally congruent family planning educational intervention, to be delivered via smart phone.
Principal Investigator: Paresh Dandona, MD, PhD, Jacobs School of Medicine and Biomedical Sciences
Co-Investigators: Gurkamal Chatta, MD, Roswell Park Comprehensive Cancer Center; Husam Ghanim, PhD, Jacobs School; Manav Batra, MD, Jacobs School; Itivrita Goyal, MD, University of Oklahoma; Manu Raj Pandey, MBBS, Roswell Park; Roberto Pili, MD, Jacobs School
Prostate cancer (PrCa) is the most common non-cutaneous malignancy among men in the United States. The mainstay treatment is androgen deprivation therapy (ADT), which reduces serum testosterone to castration level. ADT leads to development of insulin resistance and increased risk of Type 2 diabetes (T2DM) in patients with PrCa, and potential treatment options need to be identified to mitigate insulin resistance and reduce the T2DM risk and thus, associated micro- and macrovascular complications. This single-center, cross-sectional and prospective, randomized single-blinded study will investigate the role of pioglitazone treatment in reduction/reversal of insulin resistance associated with ADT in PrCa patients.
Principal Investigator: Margarita L. Dubocovich, PhD, Jacobs School of Medicine and Biomedical Sciences
Co-Investigators: Jessica L. Reynolds, PhD, Jacobs School; Sanjay Sethi, MD, Jacobs School; Gregory E. Wilding, PhD, School of Public Health and Health Professions; Alberto Monegro, MD, Jacobs School; Rajesh Kunadharaju, MD, Jacobs School; Daniel Zinkovsky, PharmD, Jacobs School
The blood of patients with COVID-19 disease shows a marked increase in the cytokines and chemokines interleukin 1β (IL-1β), interferon-γ (IFN-γ), interferon-inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), and interleukin-4 (IL-4), that together is known as the “Cytokines Storm.” Consequently, treatments that reduce cytokine/chemokine production, resulting in a less severe course of disease, could be potentially beneficial. Melatonin, a molecule produce and release primarily from the pineal gland, has been shown to have anti-inflammation, anti-oxidation, and immune-enhancing features making it an ideal treatment to counteract COVID-19 symptoms. This randomized study of 50 participants will assess the safety and efficacy of melatonin in reducing hospitalization in COVID-19 patients with mild to moderate disease.
Principal Investigators: David M. Jacobs, PharmD, PhD, School of Pharmacy and Pharmaceutical Sciences; Christopher J. Daly, PharmD, MBA, School of Pharmacy and Pharmaceutical Sciences
Established Investigator: Ekaterina Noyes, PhD, School of Public Health and Health Professions
While social determinants of health (SDoH) account for up to 90% of health outcomes, systematically identifying and addressing patients’ social needs has not historically been part of medical practice. Community health workers (CHW) are particularly effective at promoting healthy behaviors and improving health outcomes in vulnerable, underserved communities. However, accessibility to a CHW can be a barrier to those in need. This study’s researchers developed an evidence-informed toolkit to assist pharmacies in developing CHW programs and addressing SDoH in their community. This pilot study will test the feasibility of integrating a CHW program into community pharmacy settings to address SDoH for at-risk individuals.
Principal Investigator: Amit Kandel, MD, MBA, Jacobs School of Medicine and Biomedical Sciences
Co-Investigators: Michael G. Dwyer, PhD, Jacobs School; Adnan Siddiqui, MD, PhD, Jacobs School; Robert Zivadinov, MD, PhD, Jacobs School
Large vessel occlusion-related stroke has the highest rate of disability and mortality. Endovascular therapy (ET) is proven and is the most effective treatment. However, the utilization of ET has been suboptimal due to reliance on the duration of the symptoms and the perfusion imaging criteria. Functional MRI (fMRI) with resting-state fMRI (rs-fMRI), time-shift analysis (TSA-rsfMRI), and diffusion tensor imaging provide more useful functional and structural information than currently used modalities. This study will see the development and implementation of a multimodal protocol, including fMRI, to use in acute stroke intervention.
Principal Investigator: Jeffrey C. Miecznikowski, PhD, School of Public Health and Health Professions
Co-Investigators: Mohammad Nadir Haider, MD, Jacobs School of Medicine and Biomedical Sciences; Barry Willer, PhD, Jacobs School; John J. Leddy, MD, Jacobs School
Concussion is a heterogeneous mild traumatic brain injury (mTBI) characterized by a variety of symptoms, clinical presentations, and recovery trajectories. Particularly, sports-related concussion (SRC) is characterized as a concussion having occurred as a result of participating in a sport. Understanding acute and long-term consequences of SRCs has become a paramount concern within the scientific community. This study will see the creation of symptom-based clusters of SRC patients, compare clusters, assess whether there is an intervention effect (aerobic exercise vs. placebo) with time to recovery, and assess whether the data-driven clusters are reproducible in other studies.
Principal Investigator: Ekaterina Noyes, PhD, School of Public Health and Health Professions
Co-Investigators: Gregory E. Wilding, PhD, School of Public Health and Health Professions; Kathryn Glaser, PhD, Roswell Park Comprehensive Cancer Center
Modern guideline-recommended cancer survivorship care is highly specialized and requires comprehensive coordination between primary care and oncology providers. Evidence-based multidisciplinary programs for cancer survivorship mainly exist at large academic cancer centers, with rural patients having significant barriers to accessing such programs. A key gap in cancer survivorship research is understanding how to translate models of cancer care delivery developed in academic cancer centers to rural communities without widening the disparity gap. This topic has been identified as one of the NCI priorities for 2020-22. By targeting 10 community cancer centers newly affiliated with Roswell Park, this project will build a foundation and critical feasibility data for a future multi-site randomized clinical trial. This evidence is necessary to address care coordination challenges within and between care settings (e.g., between tertiary care and community settings) and coordination during transition points across the continuum of care, especially in low-income and medically underserved communities. This pilot will also improve recruitment feasibility and facilitate translating evidence about state-of-the-art cancer survivorship practices into accessible and affordable care for rural populations, with potential for reducing rural-urban disparities.
Principal Investigator: Kirkwood E. Personius, PT, PhD, School of Public Health and Health Professions
Co-Investigators: Stelios Andreadis, PhD, School of Engineering and Applied Sciences; Susan B. Udin, PhD, Jacobs School of Medicine and Biomedical Sciences
Peripheral nerves are frequently injured by trauma, resulting in permanent motor disability and sensory aberration. Why synapses fail to regain function is still poorly understood. Ectopic expression of the transcription factor NANOG in adult muscles increases the number of myogenic progenitors and induces formation of de novo muscle fibers in mice. Researchers hypothesize that NANOG expression in denervated muscle will activate additional synaptic genes compared to those previously identified in innerved adult muscles, and that induction of NANOG expression will improve functional recovery after nerve injury. This study aims to reveal the optimum duration of NANOG activation to induce reinnervation and motor function recovery.
Principal Investigator: Nikhil Satchidanand, PhD, Jacobs School of Medicine and Biomedical Sciences
Co-Investigator: Bruce Troen, MD, Jacobs School
Mild cognitive impairment is an intermediate state between the cognitive decline sometimes experienced in normal aging and severe loss of function associated with Alzheimer’s disease. Dual-task exercise, involving simultaneous performance of cognitive-motor tasks, is a distinctive, non-invasive, evidence-based therapy offering older adults a proactive strategy to improve and maintain function. Researchers have developed a home-based dual-task exercise intervention that integrates several styles of training, including patterned stepping, balance/functional training, yoga flow, and muscle strengthening combined with cognitive challenges. This study will assess changes in attention and task-switching, physical function, and dual-task performance in response to dual-task exercise training. Secondarily, researchers will collect data on participant satisfaction, enjoyment, and appeal regarding the intervention activities in order to inform development and implementation of future, larger-scale home-based trials.
Principal Investigator: Pinaki Sarder, PhD, Jacobs School of Medicine and Biomedical Sciences
Co-Investigators: John E. Tomaszewski, MD, Jacobs School; Norma J. Nowak, PhD, Jacobs School; Rabi Yacoub, MD, Jacobs School
There are still many unclear molecular players in diabetic kidney disease (DKD) pathogenesis, motivating its investigation in a broader big data context. Using machine learning tools, researchers will develop data fusion approaches for integrating histologic tissue images of DKD and molecular spatial transcriptomics data, and subsequently investigate the meaning of the resulting novel new dataspace in relation to DKD pathobiology. This blend of tissue image, cellular, and molecular information can be used to pinpoint novel disease biomarkers for improved diagnostic and therapeutic intervention strategies in DKD.
Principal Investigator: Robert M. Straubinger, PhD, School of Pharmacy and Pharmaceutical Sciences
Co-Investigators: Tista Roy Chaudhuri, PhD, School of Pharmacy and Pharmaceutical Sciences; Michael Feigin, PhD, Roswell Park Comprehensive Cancer Center; Scott Abrams, PhD, Roswell Park; Donald E. Mager, PhD, School of Pharmacy and Pharmaceutical Sciences
Pancreatic cancer (PDAC) will soon become the second leading cause of cancer death. It is refractory to most therapeutic agents, including checkpoint monoclonal antibodies. Excessive fibrosis limits access of antibodies and immune cells to PDAC tumors, and potent immune checkpoint therapeutics have failed to evoke curative immune responses in PDAC. However, stroma-targeted therapies can reduce fibrosis, improve drug delivery, and alleviate immunosuppression. This study will investigate the targeting of tumor stroma with novel immune priming strategies employing small molecule drugs and FDA-approved agents that can be repurposed expeditiously and translated clinically to reverse immune anergy in PDAC.
Principal Investigator: Thomas Suchyna, PhD, Jacobs School of Medicine and Biomedical Sciences
Co-Investigators: Carrie Miceli, PhD, UCLA School of Medicine; Christopher Ward, PhD, University of Maryland School of Medicine
Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease affecting one in every 3,500 male births worldwide. DMD is caused by a mutation that inhibits production of dystrophin, a structural protein critical for protecting muscle cells from mechanical forces. While the disease may eventually be treated by gene therapies, the current strategies are ineffective. This study aims to obtain preliminary data showing that the drug GsMTx4-D boosts current gene therapy strategies and ameliorates calcium imbalance as evidence for NIH small business grant application resubmission and further investigations into the mechanism of gene therapy improvements.
Principal Investigator: Brian Weil, PhD, Jacobs School of Medicine and Biomedical Sciences
Co-Investigators: B. Rita Alevriadou, PhD, Jacobs School; Thomas Suchyna, PhD, Jacobs School
Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure, but our poor understanding of how it develops has made it difficult to devise effective treatments. This study aims to address this problem by identifying a novel mechanism underlying HFpEF pathogenesis and establishing experimental tools to facilitate future investigation of new therapies. Researchers will evaluate the biological effects and molecular mechanisms of intraluminal pressure-induced endothelial cell dysfunction in vitro, define the role of the mechanosensitive ion channel Piezo1 in this process, and translate in vitro findings to a large animal model to demonstrate that acute pressure overload-induced microvascular dysfunction is attenuated by Piezo1 inhibition.
Funding for the CTSI Translational Science Pilot Studies Program is provided by: UB’s Office of the Provost, Office of the Vice President for Research and Economic Development, and Office of the Vice President for Health Sciences; Roswell Park Comprehensive Cancer Center; and the deans of UB’s Jacobs School of Medicine and Biomedical Sciences, School of Dental Medicine, School of Pharmacy and Pharmaceutical Sciences, School of Engineering and Applied Sciences, School of Public Health and Health Professions, and School of Nursing.