Funded Proposals

2021 Awards

Title	Cell-free DNA methylation signatures from nipple aspirate fluid for breast cancer early detection
PI/ Co-PIs/ Department	Zhang, Ke Translational Medical Sciences College of Medicine IBT Jia Li - Translational Medical Sciences
Clinical Partner	Edward Sauter, MD PhD Walter Reed Army National Medical Center 4494 Palmer Rd N Bethesda, MD 20814
Abstract	Breast cancer (BrC) is the most common cancer in women worldwide. Approximately 280,000 new cases of breast cancer are diagnosed every year in the United States, and breast cancer will be diagnosed in 12% of all women in the United States over their lifetimes. While mammography screening is helpful, it generates a high rate of false positives which require additional invasive diagnosis for validation. In order to develop an accurate non-invasive method for early BrC detection, studies are proposed to evaluate the biomarkers from nipple aspirate fluid. Successful implementation of these studies will facilitate the development of a clinical decision system for diagnosis, prevention and therapy of BrC patients.

Title	Preventing Opioid Relapse: Integrating Behavioral and Medication Treatment for Opioid Use Disorder in Jails
PI/ Co-PIs/ Department	Meagher, Mary Psychology and Brain Science College of Liberal Arts Sherecce Fields - Psychological & Brain Sciences Joy Alonzo - Pharmacy Practice Carly McCord - Psychiatry Laura Osborne - Psychological & Brain Sciences Robert Heffer - Psychological & Brain Sciences Robert Hutchison - Pharmacy Practice Theodora Chaspari - Computer Science and Engineering Annmarie MacNamara - Psychological & Brain Sciences
Clinical Partner	Kathryn Wright, RN, Medical Sergent Brazos County Detention Center 1835 Sandy Point Rd. Bryan, Texas 77807 Ph: (979) 361-4838 kwright@brazoscountytx.gov Kit@TexasJailNurse.com
Abstract	Opioid use disorder (OUD) is highly prevalent among justice-involved individuals incarcerated in jails. During incarceration, OUD often goes untreated, which increases the risk for relapse and overdose after release due to lost opioid tolerance. Consequently, opioid-related overdose mortality is the leading cause of death among people released from jails. Medication for opioid use disorder (MOUD) is an effective treatment, yet many individuals on MOUD discontinue treatment and relapse post-release. Innovative behavioral interventions are needed as an adjunct to MOUD to enhance adherence and prevent relapse. To fill this gap, we propose to develop and test the feasibility of a novel telehealth and artificial intelligence (AI)-assisted behavioral health program that targets stress, emotion dysregulation, and reward processing deficits to prevent relapse following release to the community.

Title	Tolfenamic Acid-based Therapeutic Regimen for Treatment of Pancreatic Cancer
PI/ Co-PIs/ Department	Khan, Mansoor Pharmaceutical Sciences College of Pharmacy Maen Abdelrahim - Houston Methodist Hospital/GI Medical Oncology Ziyaur Rahman - Pharmaceutical Sciences
Clinical Partner	Maen Abdelrahim, M.D., Ph.D., Pharm.B GI Medical Oncology Assistant Professor of Medicine Weill Cornell Medical College Medical Director, Cockrell Center for Advanced Therapeutics (CCAT) – Phase I Program Houston Methodist Cancer Center 6445 Main Street, Floor 24 Houston, Texas 77030 Office: 713.441.1240
Abstract	Pancreatic cancer, the fourth leading cause of cancer deaths in the United States, is a highly aggressive cancer that is typically diagnosed at an advanced stage. Despite advances in the standard, chemotherapy-based treatment, the overall prognosis for pancreatic cancer patients remains poor. Thus, new, combination strategies are needed to improve the outcome of these patients. The drug tolfenamic acid, available in Europe, Asia, and South America for the treatment of migraine headache, has been shown to inhibit pancreatic tumor growth and metastasis in laboratory tests. Based on this strong, pre-clinical evidence, we propose a clinical trial to study the safety and effectiveness of a novel combination therapy using tolfenamic acid together with standard chemotherapy for the treatment of locally advanced and metastatic pancreatic cancer.

Title	Randomized Trial of Neurosteroid Replacement Therapy for Catamenial Epilepsy
PI/ Co-PIs/ Department	Reddy, Samba Neuroscience and Experimental Therapeutics College of Medicine
Clinical Partner	Batool F. Kirmani, MD, FAAN, FAES Neurologist, Department of Neurology CHI St. Joseph Hospital 2801 Franciscan Drive Bryan, TX 77802 E-mail: bkirmani2@gmail.com
Abstract	The purpose of this clinical trial is to evaluate neurosteroid replacement therapy for controlling catamenial seizures in women with catamenial epilepsy. This is a pilot, randomized, double-blind, placebo-controlled (phase II) trial to test the efficacy and safety of oral ganaxolone as adjunctive therapy in adult women with catamenial epilepsy. After baseline screening, qualifying subjects will enter the study and be treated with drug for 7 days of perimenstrual period for 2 cycles. The primary outcome is responder rate and reduction of seizure frequency in drug vs placebo group. Presently, there is no FDA-approved therapy for catamenial seizures in women, and this trial proposes to fill this gap. The impact of the outcomes is very high in validating this new therapeutic strategy for improving women’s health.

Title	Silver Diamine Fluoride: Novel Addition to the Prophylactic Bundle for Dental Management of Radiation-Induced Dental Caries in Oral and Pharyngeal Cancer Patients
PI/ Co-PIs/ Department	Noureldin, Amal Ahmed Public Health Sciences College of Dentistry Amerian Sones - Comprehensive Dentistry
Clinical Partner	Clinical Partner: Texas Oncology-Baylor Charles A. Sammons Cancer-Center Radiation-Oncology 3410 Worth St Suite 100, Dallas, TX 75246
Abstract	Head and neck cancer has increased in Texas over the last two decades. Radiation-induced tooth decay is a devastating yet potentially preventable side effect of the cancer treatment. Silver diamine fluoride, already the standard of care in children, is inexpensive, easy to apply, and safe. The Texas A & M College of Dentistry, with partner Texas Oncology-Baylor Charles A. Sammons Cancer-Center Radiation-Oncology, proposes to conduct a preliminary clinical study (NIH Stage 0) to pilot test a randomized clinical trial of the efficacy of professionally applied 38% silver diamine fluoride to prevent tooth decay in 60 patients who are being treated with radiation for life threatening head and neck cancer. The results will benefit individual patients and provide the basis for a larger multi-center clinical trial.

Previous Awards

Nanozyme Therapy for Chronic Venous Stasis Dermatitis: New Approach for a Major Unmet Clinical Need
	Thomas A. Kent, Institute of Biosciences and Technology, Texas A&M University Mansoor A. Khan, Irma Lerma Rangel College of Pharmacy, Texas A&M University Anh Tran Tram Vo, Graduate Student, Medical Sciences, Texas A&M University Paul J. Derry, Institute of Biosciences and Technology, Texas A&M Health, Texas A&M University John P. Cooke, Houston Methodist Hospital Leslie Jenkins, Houston Methodist Hospital The goal of this project is to obtain the necessary data to successfully apply to the FDA to permit clinical studies of a new class of nano-material developed in part by Texas A&M scientists, oxidized carbon nanoparticles, to address the unmet clinical need of chronic venous stasis dermatitis. This is a common disease of the skin and veins of the lower legs that is especially prone to occur in patients with diabetes, hypertension and other cardiovascular risk factors. It has potentially debilitating complications including infection, swelling and pain. We developed a new material to specifically address a major mechanism of injury, blood vessel breakdown and chronic bleeding, which then releases toxic products that cause the cells to become dysfunctional and promote cell death (ferroptosis) and premature aging and inflammation (senescence). With this project, we believe we can develop a topical formulation that when applied to the skin will penetrate to the injury site and promote healing and speed recovery. This project maximizes the expertise of Texas A&M basic and translational science researchers and the clinical expertise of cardiovascular scientists at Houston Methodist Hospital. Successful completion will dramatically change the clinical care and prognosis of a large population of afflicted Texans and promote the building of long-term relationships and infrastructure between our institutions to facilitate development of other new therapeutics. Importantly, because the mechanisms of injury that our material addresses is also involved in many other diseases including lung and blood vessel injury due to infection, stroke and trauma, achieving FDA approval for this condition can facilitate studies in a number of other diseases that do not yet have an optimal therapy.

Nanozyme Therapy for Chronic Venous Stasis Dermatitis: New Approach for a Major Unmet Clinical Need

Thomas A. Kent, Institute of Biosciences and Technology, Texas A&M University
Mansoor A. Khan, Irma Lerma Rangel College of Pharmacy, Texas A&M University
Anh Tran Tram Vo, Graduate Student, Medical Sciences, Texas A&M University
Paul J. Derry, Institute of Biosciences and Technology, Texas A&M Health, Texas A&M University
John P. Cooke, Houston Methodist Hospital
Leslie Jenkins, Houston Methodist Hospital

The goal of this project is to obtain the necessary data to successfully apply to the FDA to permit clinical studies of a new class of nano-material developed in part by Texas A&M scientists, oxidized carbon nanoparticles, to address the unmet clinical need of chronic venous stasis dermatitis. This is a common disease of the skin and veins of the lower legs that is especially prone to occur in patients with diabetes, hypertension and other cardiovascular risk factors. It has potentially debilitating complications including infection, swelling and pain. We developed a new material to specifically address a major mechanism of injury, blood vessel breakdown and chronic bleeding, which then releases toxic products that cause the cells to become dysfunctional and promote cell death (ferroptosis) and premature aging and inflammation (senescence). With this project, we believe we can develop a topical formulation that when applied to the skin will penetrate to the injury site and promote healing and speed recovery. This project maximizes the expertise of Texas A&M basic and translational science researchers and the clinical expertise of cardiovascular scientists at Houston Methodist Hospital. Successful completion will dramatically change the clinical care and prognosis of a large population of afflicted Texans and promote the building of long-term relationships and infrastructure between our institutions to facilitate development of other new therapeutics. Importantly, because the mechanisms of injury that our material addresses is also involved in many other diseases including lung and blood vessel injury due to infection, stroke and trauma, achieving FDA approval for this condition can facilitate studies in a number of other diseases that do not yet have an optimal therapy.

New Tools for Heart Failure and Covid-19 Treatment
	Carl Tong, College of Medicine, Texas A&M University Arvind Bhimara, Houston Methodist Hospital David Zawieja, College of Medicine, Texas A&M University Gerard Coté, College of Engineering, Texas A&M University Hans Schuessler, College of Science, Texas A&M University Hubert Amrein, College of Medicine, Texas A&M University Roderic Pettigrew, College of Medicine, Texas A&M University Heart failure is a progressive chronic disease that kills ~50% of patients in 5 years and currently afflicts 6.2 million Americans. Unfortunately, the number of people suffering from heart failure is increasing throughout the United States. Covid-19 patients can suddenly deteriorate at home resulting in unexpected deaths. Texas A&M University and its clinical partners (Baylor Scott & White, CHI-St. Joseph, Houston Methodist) have united to address these two deadly diseases. Texas A&M will develop low cost mobile devices that can monitor heart function and circulatory oxygenation, thereby triggering timely interventions. Clinical partners will verify its usefulness. The overall team will incorporate the output of these devices in a database with analyses to improve treatment. The results can improve heart failure and Covid-19 care globally.

New Tools for Heart Failure and Covid-19 Treatment

Carl Tong, College of Medicine, Texas A&M University
Arvind Bhimara, Houston Methodist Hospital
David Zawieja, College of Medicine, Texas A&M University
Gerard Coté, College of Engineering, Texas A&M University
Hans Schuessler, College of Science, Texas A&M University
Hubert Amrein, College of Medicine, Texas A&M University
Roderic Pettigrew, College of Medicine, Texas A&M University

Heart failure is a progressive chronic disease that kills ~50% of patients in 5 years and currently afflicts 6.2 million Americans. Unfortunately, the number of people suffering from heart failure is increasing throughout the United States. Covid-19 patients can suddenly deteriorate at home resulting in unexpected deaths. Texas A&M University and its clinical partners (Baylor Scott & White, CHI-St. Joseph, Houston Methodist) have united to address these two deadly diseases. Texas A&M will develop low cost mobile devices that can monitor heart function and circulatory oxygenation, thereby triggering timely interventions. Clinical partners will verify its usefulness. The overall team will incorporate the output of these devices in a database with analyses to improve treatment. The results can improve heart failure and Covid-19 care globally.

Engineering Optimal Care for Patients with Heart Disease
	Michael Moreno, Texas A&M University Mahwash Kassi, Houston Methodist Hospital Byron Zambrano, Texas A&M University Darukeshwara Joladarashi, Houston Methodist Hospital Shannon Ingram, Texas A&M University Heart disease is the leading cause of death in the United States. For patients suffering from end-stage heart failure the preferred treatment option is a heart transplant. Unfortunately, the availability of donor hearts is so low that only 1 in 100 patients in need of a transplant might actually receive one at any given time. Consequently, deployment of a left-ventricular assist device (LVAD) has become the most widely employed treatment option. LVADs are essentially blood pumps that may serve as a “bridge-to-transplant”, sustaining the patient until a donor heart becomes available, or a “destination therapy” in situations wherein the patient will not receive a transplant. Though LVADs have the potential to significantly improve patient outcomes, their use has been correlated with a number of post-implant complications with 80 percent of patients experiencing at least one adverse event within two years. Among the post-implant complications, those related to the dysregulation of coagulation factors, i.e., blood borne elements that help control bleeding, are the most prevalent. The specific causes of such complications have yet to be clearly identified, though there is evidence they result from the effects the LVAD has on cardiac hemodynamic patterns, which in turn depends on the specific way in which the LVAD components are deployed into the ventricle and the aorta. The goal of this project is to use patient-specific imaging data to develop an experimentally validated computational model to investigate the correlation between LVAD implementation and post-implant complications. The computational framework will enable patient-specific deployment options to be simulated as part of the surgical planning process. The potential impact is significantly improved reliability of LVAD therapy across the patient population and full realization of the potential of LVAD therapy as a viable alternative to heart transplant.

Engineering Optimal Care for Patients with Heart Disease

Michael Moreno, Texas A&M University
Mahwash Kassi, Houston Methodist Hospital
Byron Zambrano, Texas A&M University
Darukeshwara Joladarashi, Houston Methodist Hospital
Shannon Ingram, Texas A&M University

Heart disease is the leading cause of death in the United States. For patients suffering from end-stage heart failure the preferred treatment option is a heart transplant. Unfortunately, the availability of donor hearts is so low that only 1 in 100 patients in need of a transplant might actually receive one at any given time. Consequently, deployment of a left-ventricular assist device (LVAD) has become the most widely employed treatment option. LVADs are essentially blood pumps that may serve as a “bridge-to-transplant”, sustaining the patient until a donor heart becomes available, or a “destination therapy” in situations wherein the patient will not receive a transplant. Though LVADs have the potential to significantly improve patient outcomes, their use has been correlated with a number of post-implant complications with 80 percent of patients experiencing at least one adverse event within two years. Among the post-implant complications, those related to the dysregulation of coagulation factors, i.e., blood borne elements that help control bleeding, are the most prevalent. The specific causes of such complications have yet to be clearly identified, though there is evidence they result from the effects the LVAD has on cardiac hemodynamic patterns, which in turn depends on the specific way in which the LVAD components are deployed into the ventricle and the aorta. The goal of this project is to use patient-specific imaging data to develop an experimentally validated computational model to investigate the correlation between LVAD implementation and post-implant complications. The computational framework will enable patient-specific deployment options to be simulated as part of the surgical planning process. The potential impact is significantly improved reliability of LVAD therapy across the patient population and full realization of the potential of LVAD therapy as a viable alternative to heart transplant.

Roles of Salivary Macrophage-related Soluble Factors in Radiotherapy-induced Dry Mouth
	Fei Liu, Molecular and Cellular Medicine Scott Goble, CHI St. Joseph Health Debbie Lewis, CHI St. Joseph Health Head and neck cancers are diagnosed in about 70,000 new cases each year in USA, and are often treated with radiation involving healthy salivary glands. Such a radiation therapy commonly results in the lasting and severe decrease of saliva secretion. The consequent dry mouth remarkably impairs the quality of life and is extremely difficult to cope with. As indicated by our animal studies, one previously unknown mechanism of this side effect is the decrease of local immune cells termed macrophages and related soluble factors essential for the function of salivary gland. The goal of this project is to determine whether levels of these soluble factors in saliva of head and neck cancer patients are affected by radiation therapy and related to dry mouth. This project will reveal novel mechanisms of lasting dry mouth after radiation therapy and build the basis for developing effective treatments of this side effect.

Roles of Salivary Macrophage-related Soluble Factors in Radiotherapy-induced Dry Mouth

Fei Liu, Molecular and Cellular Medicine
Scott Goble, CHI St. Joseph Health
Debbie Lewis, CHI St. Joseph Health

Head and neck cancers are diagnosed in about 70,000 new cases each year in USA, and are often treated with radiation involving healthy salivary glands. Such a radiation therapy commonly results in the lasting and severe decrease of saliva secretion. The consequent dry mouth remarkably impairs the quality of life and is extremely difficult to cope with. As indicated by our animal studies, one previously unknown mechanism of this side effect is the decrease of local immune cells termed macrophages and related soluble factors essential for the function of salivary gland. The goal of this project is to determine whether levels of these soluble factors in saliva of head and neck cancer patients are affected by radiation therapy and related to dry mouth. This project will reveal novel mechanisms of lasting dry mouth after radiation therapy and build the basis for developing effective treatments of this side effect.

Combining Low Dose Computerized Tomography and Blood-Based Biomarkers of Genetic Instability to Impr
	Kenneth S. Ramos, Texas A&M Health, Texas A&M University Randa El-zein, Houston Methodist Hospital Nestor F. Esnaola, Houston Methodist Hospital Ke “Kurt” Zhang, College of Agriculture and Life Sciences Chronic obstructive pulmonary disease (COPD) affects ~24 million people in the U.S. Most of these patients are at high risk of developing lung cancer and eligible for low dose- computerized tomography (LDCT) screening. While LDCT screening is helpful, challenges remain including a high rate of false positives and the need to screen large number of smokers to prevent one lung cancer death. In addition, the inherent cancer genetic susceptibility of the patient has not been integrated into the selection of those who would benefit most from screening. To fill these major gaps in patient care, studies are being conducted to evaluate the utility of blood-based biomarkers of genetic instability to distinguish between high-risk and low-risk COPD patients to improve the clinical utility of LDCT screening for lung cancer. Successful clinical roll out of this program can help identify patients requiring focused intervention for early diagnosis and cancer prevention.

Combining Low Dose Computerized Tomography and Blood-Based Biomarkers of Genetic Instability to Impr

Kenneth S. Ramos, Texas A&M Health, Texas A&M University
Randa El-zein, Houston Methodist Hospital
Nestor F. Esnaola, Houston Methodist Hospital
Ke “Kurt” Zhang, College of Agriculture and Life Sciences

Chronic obstructive pulmonary disease (COPD) affects ~24 million people in the U.S. Most of these patients are at high risk of developing lung cancer and eligible for low dose- computerized tomography (LDCT) screening. While LDCT screening is helpful, challenges remain including a high rate of false positives and the need to screen large number of smokers to prevent one lung cancer death. In addition, the inherent cancer genetic susceptibility of the patient has not been integrated into the selection of those who would benefit most from screening. To fill these major gaps in patient care, studies are being conducted to evaluate the utility of blood-based biomarkers of genetic instability to distinguish between high-risk and low-risk COPD patients to improve the clinical utility of LDCT screening for lung cancer. Successful clinical roll out of this program can help identify patients requiring focused intervention for early diagnosis and cancer prevention.

Improving Maternal Healthcare Equity and Reducing Racial Disparities in Maternal Health Outcomes
	Theresa M. Morris, College of Liberal Arts, Texas A&M University Vani Mathur, College of Liberal Arts, Texas A&M University Ping Ma, School of Public Health, Texas A&M University Elizabeth Wells-Beede, College of Nursing, Texas A&M University Hector Chapa, CHI St. Joseph Health Regional Hospital Disparity in labor pain experience and higher maternal morbidity and mortality rates in Black women are major public health problems in the U.S., which are exacerbated by a lack of comprehensive research. Therefore, we will collaborate with CHI St Joseph Hospital to exam labor pain disparity and the role of pain as a predictor of racial disparity in maternal morbidity and mortality. The proposed interdisciplinary research is expected to lead to the development of novel translational research and health promotion interventions in the clinical setting, which can be disseminated to other Texas hospitals to improve the maternal healthcare quality and health outcomes by decreasing racial and socioeconomic class disparities in maternal morbidity and mortality and in maternal labor pain experiences.

Improving Maternal Healthcare Equity and Reducing Racial Disparities in Maternal Health Outcomes

Theresa M. Morris, College of Liberal Arts, Texas A&M University
Vani Mathur, College of Liberal Arts, Texas A&M University
Ping Ma, School of Public Health, Texas A&M University
Elizabeth Wells-Beede, College of Nursing, Texas A&M University
Hector Chapa, CHI St. Joseph Health Regional Hospital

Disparity in labor pain experience and higher maternal morbidity and mortality rates in Black women are major public health problems in the U.S., which are exacerbated by a lack of comprehensive research. Therefore, we will collaborate with CHI St Joseph Hospital to exam labor pain disparity and the role of pain as a predictor of racial disparity in maternal morbidity and mortality. The proposed interdisciplinary research is expected to lead to the development of novel translational research and health promotion interventions in the clinical setting, which can be disseminated to other Texas hospitals to improve the maternal healthcare quality and health outcomes by decreasing racial and socioeconomic class disparities in maternal morbidity and mortality and in maternal labor pain experiences.

Review Panel Roster

PCRP A President's Excellence Fund Initiative

PCRP

PCRP

Funded Proposals

2021 Awards

Previous Awards