UH Drug Discovery Institute

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.