UH Drug Discovery Institute

The future of cardiovascular research is beating strong at University of Houston (UH) laboratories, where 15 undergraduate students spent the summer gaining paid hands-on experience, learning from expert mentors and contributing to research aimed at advancing heart health.

Funded by the American Heart Association and the National Institutes of Health, respectively, the UH-Houston Experience for Advancing Research and Training (UH-HEART) and the UH-Cardiovascular Undergraduate Research Experience (UH-CURE) programs culminated in a successful showing of student research at various conferences. Among these were the American Heart Association’s Basic Cardiovascular Sciences (BCVS) Scientific Sessions July 13-16 in Boston; the UH College of Pharmacy (UHCOP) PPS Research Symposium; and the end-of-year presentations. Both UH-HEART and UH-CURE programs are directed by UHCOP Professor and Assistant Chair of the Department of Pharmacological and Pharmaceutical Sciences Bradley McConnell, Ph.D., FAHA.

Connecting with the Cardiovascular Research Community

The AHA conference connected the participants with approximately 60 undergraduate cardiovascular researchers from across the country. Alongside students conducting summer research at 11 universities and research institutions, they presented their findings through poster sessions, answering questions and discussing their work with attendees and judges.

“Even though people attended with varying levels of experience and expertise, the sessions felt approachable and welcoming,” said Jenevieve Lopez, UH-CURE participant from Occidental College in Los Angeles. “I was able to learn from highly scientific presentations while still finding talks that were relevant and accessible to me as an undergraduate researcher.”

Participants also attended scientific lectures and early-career development sessions as well as an the exclusive “Lunch with the Legends” event, gaining career guidance and mentorship through small-group conversations with distinguished scientists and physicians.

“The conference helped me realize that presenting research is not just about explaining results but also learning from the questions and ideas of others,” said Nishi Modi, UH-HEART participant from University of Texas at Arlington."

The UH-CURE participants and their research presentations were:

• Katarina Dobrosky, Wake Forest University, “Membrane-Associated Transcription Factor MYRF Regulates Epicardial Cell Migration to Drive Cardiac Dysfunction and Hypoplastic Left Heart Syndrome”
• Oscar Garza, The University of Texas at Austin, “Talin: Integrin Activation and Disruption”
• Erin He, Rice University, “TAK1 Regulates Multiple Oncogenic Signaling Pathways and Mitochondrial Stress Responses in Rhabdomyosarcoma”
• Ali Irhabi, University of Houston, “STEMIN- and YAP5SA-Induced Exosomes as a Therapeutic Strategy to Block Cell Death in Failing Hearts”
• Ethan Liu, Case Western Reserve University, “Comparative Characterization of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells with Human Umbilical Vein Endothelial Cells”
• Jenevieve Lopez, Occidental College, “Investigating the Effect of AKAP12 Upregulation on AKAP5 in Cardiac β-Adrenergic Signaling”
• Camila Leonor Madera Ruiz, Universidad de Puerto Rico en Ponce, “Cardiovascular Drug Repurposing to Prevent BTK Inhibitor-Induced Endothelial Dysfunction”
• John Nguyen, Texas A&M University (College Station), “Aptamer-Conjugated Polymers for Targeting Cardiovascular Disease”
• Bailey Perry, Howard University, “Impact of Antipsychotics on Cardiovascular Outcomes Among Older Adults with Dementia”
• Esther Umezurike-Chukwu, Case Western Reserve University, “Effects of Prior LPS Exposure on Adipose Macrophage Inflammation and Diabetes Risk”

The UH-HEART participants and their research presentations were:

• Adam Alubaidi, University of Houston, “Determining the Molecular Changes in Mice Hearts After a Single Bout of Treadmill Running”
• Allison Ding, Rice University, “Developing Optimized Bioprinting Techniques for Cardiac Tissue Chip Applications”
• Elaine Liu, The University of Texas at Dallas, “Development and Characterization of a Tantalum-Loaded Self-Assembling Peptide Hydrogel for Endovascular Embolization”
• Nishi Modi, University of Texas at Arlington, “HSL Inhibition Affects Oleic Acid-Induced Lipid Droplet Accumulation in Mouse Cardiac Endothelial Cells”
• Anna Toombs, Tougaloo College, “Investigating BAF60a’s Role in Endothelial Cell Dysfunction”

National Recognition

Ethan Liu and Nguyen earned first and fourth place awards for their posters, while UH received an AHA Institutional Award for Undergraduate Student Training for the UH-HEART program, which provided additional support to its participants.

McConnell and the UH-HEART/UH-CURE undergraduates were also joined at the AHA meeting by UHCOP's Ying Xu, Ph.D. candidate, and Luqi Zhao, Ph.D., postdoctoral fellow, who received BCVS New Investigator Travel Awards to present posters at the meeting. Xu's project was on "Compartmentalized cAMP Dysregulation by the AKAP12-PDE8A Axis Drives Electrical Remodeling and Heart Failure” and Zhao's project was on "Pathogenesis of acquired left ventricle non-compaction."

In addition to the AHA meeting, UH-HEART and UH-CURE undergraduates also presented their research July 31 at UHCOP, which concluded both summer research programs, and some were able to also present at the annual PPS Research Symposium hosted by UHCOP's Department of Pharmacological and Pharmaceutical Sciences Aug. 13-14.

“It was an honor to mentor these 15 outstanding undergraduate researchers,” McConnell said. “Our cohort included talented students from UH, universities across Texas, and institutions nationwide. Their projects spanned basic, translational, and applied sciences, as well as population-based research, highlighting the breadth of cardiovascular research conducted across UH faculty laboratories.”

On March 26, the UH Drug Discovery Institute hosted Dan Monticello of GlycosBio for a research seminar titled “Lipid Engineering to Create New Therapeutics and Other Useful Products.”

In this talk, Monticello described enzyme-based processes to enhance the nutritional and therapeutic properties of lipids— plant and animal fats. GlycosBio has developed a library of proprietary lipids designed to enhance the performance of personal care molecules, including the ability to selectively unlock antimicrobial properties of natural materials for therapeutic benefit.

Studies show improved bioavailability in oils for cystic fibrosis patients and species-specific antimicrobial activity for rebalancing microbiomes. Studies have also targeted strep throat, RSV, and dental caries. Monticello also described how lipids may be engineered to interact with the skin, increasing their permeability to a range of hydrophobic molecules from hydrocortisone to CBD. Vegetable oils can also be modified to act as latex-compatible lubricants to replace silicone oils.

Daniel J. Monticello, Ph.D. is Chief Scientific Officer at GlycosBio Inc. in the Texas Medical Center. He obtained his B.S. in Microbiology from the University of Michigan and a Ph.D. from Michigan State University. He completed his postdoctoral training at the University of Georgia before joining Miles Laboratories in Indiana. Monticello has co-founded several biotechnology companies. He is inventor or co-inventor on over 40 issued or pending U.S. patents.

On November 15, an online webinar given by Heather Caslin, Ph.D., professor in the UH Health and Human Performance Department, asked the question: is weight loss always good?

Caslin’s research suggests that while weight loss is good for metabolic health, the immune cells in fat tissue appear to “remember” former weight gain. The immune cell populations that infiltrate into the fat, expand with, and activate upon weight gain are retained following weight loss. These cells are known to contribute to insulin resistance and the development of diabetes.

Moreover, Dr. Caslin showed that adipose macrophages specifically develop innate immune memory, or trained innate immunity, which primes them for enhanced activation to bacterial stimuli like LPS or to regain weight. Cycles of weight gain and loss increase risk for diseases like diabetes and hypertension when compared to stable weight gain, and thus, adipose macrophage memory may play a causal role in weight cycling- accelerated disease risk.

Weight cycling is very common, as weight loss is hard to do and hard to maintain. Thus, Caslin’s research helps us to understand one mechanism by which weight cycling may worsen disease risk. Moreover, it suggests that adipose macrophage memory may be a potential therapeutic target in weight cycling- accelerated diabetes.

The Vanderbilt Institute of Chemical Biology (VICB) was established in 2002 with the stated mission to establish research and education programs in the application of chemical technologies to important biological problems. A large percentage of Nobel Prizes, in fact, are chemical biology-related. 

In his seminar to the UH Drug Discovery Institute, Gary A. Sulikowski of VICB gave an historical introduction to the Institute and provided select examples of chemical probes developed within the VICB. Chemical probes are powerful tools that modulate the activity of specific proteins in cells often with the goal of demonstrating disease relevance. They are potential pathfinder molecules for drug discovery.

Challenging efforts in pre-clinical development were discussed, such as apoptolidin family glycomacrolides which target leukemia through inhibition of ATP synthase. Of much interest to the participants: Vanderbilt’s high-throughput screening facility, which allows faculty and students to conduct small molecule and drug screenings, functional genomics screening and high content screening. The VICB also houses a compound library.

Sulikowski received a BS in chemistry from Wayne State University and a Ph.D. in organic chemistry from the University of Pennsylvania. He was an American Cancer Society postdoctoral fellow at Yale University. His first faculty appointment was in the Department of Chemistry at Texas A&M University in 1991, and he joined the Vanderbilt Chemistry Department and Institute of Chemical Biology in 2004. Sulikowski’s research interests involve the design and development of chemical syntheses of complex molecules, specifically bioactive natural products and molecular probes. Over time his interests have expanded to the chemical synthesis of molecular tools with application in biological research and therapeutic lead development. He has published over 125 research publications and co-authored 11 patents.

On May 25, the University of Houston Drug Discovery Institute hosted Wei Li, Ph.D. for a hybrid seminar entitled: "The Discovery of a New Generation of Tubulin Inhibitors for Metastatic Cancer.” 

Li, Distinguished Professor at the University of Tennessee Health Science Center (UTHSC), the Director of the UTHSC College of Pharmacy (UTCoP) Drug Discovery Center, and the Faculty Director of the Shared Analytical Instrument Facility at UTCoP, provided a comprehensive overview of groundbreaking research on orally bioavailable tubulin inhibitors. This research has demonstrated exceptional efficacy in combating cancer and shows great promise in overcoming drug resistance mechanisms.

Li's work represents a significant advancement in the field of cancer treatment, specifically in addressing the limitations associated with widely used tubulin inhibitors such as paclitaxel. By specifically targeting the colchicine binding site, these novel inhibitors exhibit a broad spectrum of potent anticancer activity. Notably, the investigational new drug Sabizabulin, derived from Li's research, has progressed to multiple clinical trials for cancer treatment. In addition, it recently also completed a Phase 3 trial for hospitalized COVID-19 patients. 

Moreover, Li shared valuable insights into the ongoing project in his lab, which focuses on the discovery of selective TRPC3 inhibitors for the treatment of neurological diseases, particularly epilepsy. This ongoing research endeavors to identify compounds that can effectively modulate TRPC3 channels and hold the potential to address unmet medical needs in the field of neurological diseases.