UH Drug Discovery Institute

With nearly $1 million in federal funding, a University of Houston researcher will study the connection between an enzyme found in cancerous tumors and immune cells of lupus patients — innovative research that could transform how lupus is diagnosed and treated.

Awarded September 1 from the U.S. Department of Defense, the $999,932 grant will support the work of Associate Professor Dr. Weiyi Peng, whose research aims to reshape understanding of lupus biology, improve patient monitoring and potentially accelerate treatment by repurposing existing cancer drugs.

Lupus, or systemic lupus erythematosus, is a chronic autoimmune disease in which immune cells mistakenly attack healthy tissue. The disease — which can affect the kidneys, heart, lungs, skin, joints or brain — impacts an estimated 1.5 million Americans and at least 5 million people worldwide, according to the Lupus Foundation of America.

“With this funding, we can make our idea eventually translate into the clinical setting and benefit more lupus patients,” said Peng, who directs both the Drug Discovery Institute and Center for Nuclear Receptors and Cell Signaling at UH.

Explaining the Mechanisms

Associate Professor Dr. Weiyi Peng (third from right) poses with her team for a portrait. Order of team from left to right: Debanwita Burman, Chitra, Ashley Guerrero, Weiyi Peng, Jiakai Hou and Ningbo Zheng.

Peng’s work builds on her background in cancer immunology. In previous studies, she found that many tumors overexpress protein arginine methyltransferase 5 (PRMT5), an enzyme that alters the function of other proteins and promotes tumor growth when abnormally elevated.

Recent studies show that PRMT5 is also overactive in the immune cells of lupus patients and mouse models, leading Peng to believe the enzyme may play a critical role in lupus profession. Over the next four years, her team will:

• Determine whether PRMT5 inhibitors — already in clinical trials for cancer — can slow or reduce lupus disease progression.
• Investigate whether PRMT5-modified proteins generate new autoantibodies that could serve as biomarkers to diagnose lupus, assess disease severity and monitor treatment response.

The Bigger Picture

Peng will collaborate with Dr. Chandra Mohan — a leading lupus researcher at UH — and physicians from UT Southwestern Medical Center and UTHealth Houston. Together, the multidisciplinary team will study archived samples from approximately 100 lupus patients.

“This is definitely a team effort with different multidisciplinary experts to eventually ensure the success of the project,” Peng said.

Peng is one of two UH researchers to receive federal funding this year for lupus research. Biomedical engineer Tianfu Wu received a $1 million Impact Award from the DOD to develop a new drug delivery system that targets the spleen, where certain immune cells contribute to lupus.

Accelerating advancements in cancer prevention and cures, Wei Gao, assistant professor of pharmacology at the University of Houston College of Pharmacy, has received a $900,000 grant from the Cancer Prevention and Research Institute of Texas to develop stronger and more targeted anti-tumor therapy for pancreatic and lung cancer.

Pancreatic and lung cancers are among the deadliest cancers, partly because they create an environment that shields tumors from the immune system. One key player in this immune suppression is the regulatory B cell (Breg) — a type of immune cell that actually helps tumors grow by blocking the body’s natural defenses.

Wei Gao, assistant professor of pharmacology, center, with her team of doctoral students and post-doctoral fellows (l-r) Dan Wang, Xinxin Deng, Jenny Hu and Feixiang Chen.   

Some newer treatments, called STING agonists, are meant to activate the immune system but have limited success because they unintentionally increase Bregs, don’t reach tumors effectively and can cause serious side effects.

“To address these challenges, our team developed Nano-273, a dual-function nanodrug packaged in a tiny albumin-based particle. Nano-273 both activates STING and blocks PI3Kγ—a pathway that drives Breg expansion, while albumin nanoparticles help deliver the drug directly to immune cells, reducing unwanted side effects,” said Gao. “This approach reduces harmful Bregs while boosting immune cells that attack cancer, leading to stronger and more targeted anti-tumor responses.”

In early studies, Nano-273 showed strong tumor-shrinking effects in pancreatic and lung cancer models, especially when combined with chemotherapy or immunotherapy. It also extended survival and showed low toxicity.

To move these promising results closer to clinical use, Gao’s team will carry out several critical preclinical steps:

• Improve the production of Nano-273, ensuring it is consistently made with high quality for future clinical trials
• Test how well Nano-273 works when combined with standard treatments like chemotherapy and immune checkpoint inhibitors in pancreatic and lung cancer models
• Conduct safety studies

“If successful, this project could lead to a new type of immunotherapy that offers lasting tumor control and improved survival for patients with pancreatic and lung cancers, two diseases that urgently need better treatments,” said Gao.

Since 2007 when it was established by the Texas Legislature, CPRIT has invested in the research prowess of Texas universities and research organizations; created and expanded life science infrastructure across the state; expedited innovation in research; and enhanced the potential of breakthroughs in cancer prevention and cures.

On March 5, the University of Houston Drug Discovery Institute hosted John Buolamwini, Ph.D. for a research talk entitled: “Discovery and Optimization of Small Molecule Drug Leads and Probes.”

Buolamwini's multidisciplinary approach integrates synthetic medicinal chemistry, computational modeling, and experimental techniques to target a variety of chronic diseases, including ischemic heart disease, cancer, HIV/AIDS and Alzheimer’s. 

Buolamwini’s talk opened with a discussion of human concentrative nucleoside transporters (hCNTs) and the necessity of understanding their structure. Buolamwini explained how homology models for hCNT1, hCNT2, and hCNT3 were constructed using the crystal structure of a similar transporter in Vibrio cholerae bacteria as a template. Validation of these models was conducted through docking experiments with known inhibitors, revealing promising correlations, particularly for hCNT1. Subsequent virtual screening using the hCNT1 model identified 14 new inhibitors, showing the potential of these methods in drug discovery targeting nucleoside transporters. 

Buolamwini also discussed another area of his research which focuses on targeting  the constantly active STAT3 pathway in Glioblastoma (GBM), a tumor affecting the brain or spine. Buolamwini introduced SS-4, a novel small molecule designed to disrupt the STAT3-SH2 domain interaction. Computational modeling demonstrated SS-4's efficacy in blocking the activation of the STAT3 protein at low concentrations. In vitro studies confirmed SS-4's ability to suppress GBM cell proliferation and induce apoptosis (i.e., cell death), and in vivo experiments highlighted the potential of SS-4 as a therapeutic agent for GBM treatment. 

Throughout the talk, Buolamwini emphasized the importance of interdisciplinary collaboration in addressing complex medical challenges. His innovations in drug design and discovery offer a promising outlook for improved patient outcomes through the development of novel therapeutics. 

John Buolamwini, Ph.D. is chair of Pharmaceutical Sciences at Rosalind Franklin University. He has held faculty positions in the United States for the past 30 years, including the University of Mississippi and the University of Tennessee, where he served as the Vice Chair and Director of Graduate Programs of the Department of Pharmaceutical Sciences from 2012-2014. 

A University of Houston engineering professor is examining the life cycle of stubborn, drug-resistant persister cells in recurrent infections to find a way to destroy them. Persister cells are non-growing cell subpopulations observed in many pathogenic bacteria and they certainly live up to their name – they persist, and are not fazed by current medications. Scientists believe they cause the recurrence of chronic health issues like airway infections in cystic fibrosis patients, urinary tract infections and tuberculosis.

“If we know how persister cells are formed, we can target their formation mechanisms to eliminate these dangerous cell types,” said Mehmet Orman, assistant professor of chemical and biomolecular engineering, who is using a $1.9 million grant from the National Institute of Allergy and Infectious Diseases to explore persister cells.

Orman believes that self-digestion, or autophagy, stimulates persister formation. In self-digestion, cells recycle essential energy molecules by eating their own protein, lipids or other bits to stay alive or temporarily survive under starvation conditions. Self-digestion is triggered by extracellular stress conditions, such as nutrient depletion, hypoxia and overpopulation.

Orman will map the self-digestion-related mechanisms in E. coli to understand how self-digestion is linked to persister cell formation. Then, he will therapeutically explore these mechanisms to identify chemical compounds that can eliminate persister cells.

“Mapping of this comprehensive bacterial pathway from its initial exogenous trigger, through its signal transduction, to the source of antibiotic tolerance, will enable us to develop affective anti-persister therapeutics,” said Orman.

Self-digestion inflicts damage on the cells and can make the cells dormant, putting them in a sleeping mode, and these dormant cells are not effected by antibiotics. The bacterium is less fit to produce protein and resume growth upon exposure to fresh nutrients, providing temporary protection against antibiotics until the self-inflicted damage is repaired. 

From an evolutionary perspective, self-digestion is an important survival mechanism. This complex process, which is orchestrated by many regulatory proteins and enzymes, has been well documented in mammalian cells, but largely ignored in bacteria. “By integrating our expertise in bacterial cell biology with advanced current technologies, we aim to decipher the key components of this pathway to provide a clear and much-needed picture of bacterial self-digestion mechanisms,” said Orman.

Orman, himself, is persistent. Previously he developed methods to directly measure the metabolism of persister cells. He has also discovered that persisters are mostly derived from stationary-phase cells with high metabolic activities maintained by self-digestion.

On Tuesday, April 23, the UH Drug Discovery Institute hosted Sharath Hegde of Congruence Therapeutics for a research talk titled “Discovering Impactful Medicines: Many Paths, Same Goal.” 

Hegde’s talk opened with an overview of the drug development process, in which he contextualized high attrition rates in pre-clinical and clinical testing phases. While there are over 1,000 drug companies internationally, only 55 novel drugs were approved by the Food and Drug Administration in 2023. Hegde estimated that for every 100,000 potential compounds for novel drugs, only one is demonstrated to be safe and efficacious in the target patient population at the intended therapeutic dose. 

The talk then transitioned into a discussion of four different paths to drug discovery— phenotypic screening, repurposing existing drugs, utilizing a fast-follower approach and taking a target-driven approach. For each method of drug discovery, Hegde described in detail case studies of approved medicines and shared insights from his own drug development experiences. The seminar concluded with practical considerations for drug-hunting, such as decision-making with imperfect data and optimizing optionality and focus. 

Sharath S. Hegde, Ph.D. is Chief Scientific Officer at Congruence Therapeutics and a passionate drug hunter who has participated in the discovery of several NCEs including the marketed medicines Vibativ® (telavancin), Yupelri® (revefenancin) and Aloxi® (palanosetron). He obtained his Ph.D. in Pharmacology from the University of Houston. Hegde has extensive experience in seeding new project ideas and driving the discovery of first-in-class/best-in-class drugs in multiple therapeutic areas including cardiovascular, respiratory, genitourinary and gastrointestinal diseases. He is the co-author of over fifty scientific publications. 

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.

The University of Houston Drug Discovery Institute supports innovative drug discovery and development research through its Seed Grant Program. This year, three multidisciplinary research teams have been selected to receive funding to develop competitive extramural grant proposals, advancing UH’s research priority area of Health and Well-being. 

New to the program, DDI included a separate Technique Expansion Track for projects that would leverage the state-of-the-art equipment in UH core facilities to strengthen external grant applications in drug discovery. Two proposals were awarded for the technical track. 

Each winning team will receive funding to support critical activities like pilot studies, data collection, and proposal development. 

2025 DDI Seed Grant Recipients 

Scientific Track: $50,000 

1. A Novel Closed-System Microfluidic Platform for High-Purity Lymphocyte Isolation from Whole Blood: Enhancing PSMA-Targeted CAR T Therapy for Prostate Cancer
   1. Team: Sergey Shevkoplyas, Cullen College of Engineering ; Qin Feng, College of Natural Sciences and Mathematics
2. Mechanistically Novel Inhibitors of Androgen Receptor to Treat Prostate
   1. Team: Alexander V. Statsyuk, College of Pharmacy ;Tasneem Bawa-Khalfe, College of Natural Sciences and Mathematics
3. Studies on the Mycobactericidal Properties of Lysates from an Actinobacterial Isolate Tersicoccus Phoenicis
   1. Team: William Widger and  Madhan Tirumalai, College of Natural Sciences and Mathematics; Patrick Cirino, Cullen College of Engineering 

Technique Expansion Track: $15,000 

1. Improving CAR T Therapy Efficacy and Persistence through Modulation of a Transcriptional Coactivator
   1. PI: Qin Feng, College of Natural Sciences and Mathematics
2. Novel Targeted Therapy for Vasculopathy in Cryopyrin-associated Periodic Syndrome
   1. PI: Yunting Wang, College of Pharmacy 

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.