2026-2027 Gateway Awardees

Katherine Cook, Ohio Northern University

Mentor: Dr. Dalia Abdelhamid

Research Title: Development of Novel Indole-Chalcone Hybrids as Potential Anticancer Agents: Design, Synthesis, and Anticancer Screening

“Our research begins by designing new molecules, using indole and chalcone scaffolds. We chose indole and chalcone as the building blocks for these molecules, because they have strong anticancer properties.  By combining these two structures into one hybrid molecule, we aim to create compounds that are more powerful than either structure alone. We use computer models, past research experience, and chemistry knowledge to design these indole-based chalcone hybrids and predict how they might work against cancer cells. After designing, the next step is to make these compounds in the lab. We do this by combining different chemicals in a controlled environment, similar to following a recipe used to cook a meal. Once we have created our molecules, we use advanced tools to make sure we made the correct compound, similar to a taste test of a meal. This helps confirm that the molecule we made is pure and ready to move on to testing.

The synthesized hybrids will be subjected to various tests to reveal how well they can kill cancer cells and whether they are selective (targeting cancer cells but not normal cells). We will test the compounds in laboratory cancer cell cultures to see if the drugs can stop cancer cells from growing or make them die and investigate how they work in the cell. We will analyze the data from testing to identify hybrid(s) that are effective at killing cancer cells while causing the least harm to healthy cells. The team hopes to identify at least one or two lead compounds with strong potential as anticancer drugs which could serve as starting points for further development and testing, including animal studies to see if they are safe and effective in a living organism.

In summary, the project aims to create new cancer-fighting drugs by designing, making, and testing indole and chalcone hybrids. What sets this research apart is the combination of these two highly promising chemical scaffolds into one hybrid molecule, which could result in a “double attack” on cancer cells. By targeting cancer through multiple mechanisms, the hybrids may be more effective and less likely to allow cancer cells to develop resistance, a common problem in cancer treatment. ”

Paramjit Kaur, University of Maryland

Mentor: Dr. Susan dosReis

Research Title: Evaluating the Value of GLP-1 Receptor Agonists for Antipsychotic-Induced Weight Gain in Youth Initiating Second-Generation Antipsychotics

“The objective of this study is to develop a patient-centered value assessment of the clinical and economic trade-offs of GLP-1 RAs as adjunctive therapy to mitigate antipsychotic-induced weight gain in youth. This study has two aims. The first aim is to quantify caregiver preferences for using GLP-1 RA medications to reduce antipsychotic-induced weight gain. The second aim is to assess the clinical and economic value of GLP-1 RA from the patient and family perspective.

We will conduct a survey that will be available online.  The survey will measure the elements of clinical benefit and cost that influence preferences for using a GLP-1 RA. The study subjects will be the primary caregiver of a child aged 5–21 years old and who may have used an antipsychotic medication and who resides in the United States.  Study subjects will be recruited using a patient panel called ResearchMatch. The panel includes individuals across the United States. The survey will also collect demographic information on the caregivers and their child, healthcare service use, mental health diagnoses, duration on an antipsychotic, use of adjunctive medication for antipsychotic-induced weight gain, and any other concurrent medication treatments. Patient preferences will be used to assess the economic impact and value of GLP-1 RA on preventing obesity among youth prescribed an antipsychotic.

This study will provide evidence on the value of GLP-1 RA initiation in youth treated with SGAs, addressing a critical gap in pediatric management of SGA-induced weight gain. This research will inform future clinical guidelines.” 

Blake Lewis, High Point University

Mentor: Dr. Comfort Boateng

Research Title: Design and Synthesis of Highly Selective Ligands for Dopamine D4 Receptor to Treat Neuropsychiatric Disorders

“Drug and alcohol addictions affect more than 22 million people in the United States alone. Abuse of tobacco, alcohol, and illicit drugs is costing the US more than $740 billion annually in costs related to crime, lost work productivity and health care reported by NIDA/NIH.  The research is on the development of new antagonist ligands for Dopamine D4 Receptor to treat Substance Use Disorders. The identification of effective FDA-approved medications for the treatment of psychostimulant addiction presents a public health challenge, as available therapeutic options are exclusively behavioral. Among psychostimulant drugs, cocaine has considerable abuse potential in its indirect ability to enhance the mesolimbic dopamine reward circuit via inhibition of presynaptic reuptake transporters of the neurotransmitter. Previous studies have evaluated the efficacy of D1, D2, and D3 receptor antagonists, and though they have not yet yielded a treatment, they have contributed to a better understanding of the delineation of the neurocircuitry disrupted in addiction. The purpose of this research study is to design and synthesis of highly selective D4R antagonist ligands to treat addiction.” 

Manali Patel, Temple University

Mentor: Dr. Patrick Glassman

Research Title: Investigating the Role of Acyl Chain Length on the Pharmacology of Fatty Acid-Tagged Thrombin Inhibitors

“The proposed research project is to develop relationships between the size of fatty acids attached to bivalirudin and key pharmacology outcomes for bivalirudin.  Manali will use a conjugation strategy that she has previously optimized to attach fatty acids with a range of sizes (8 – 20 carbons) to bivalirudin and will confirm conjugation using size exclusion chromatography.  She will characterize the in vitro activity of the conjugate in the following settings: 1) impact on thrombin activity using a probe substrate and 2) impact on in vitro clot formation in the presence and absence of albumin (the binding partner of fatty acids).  The next stage of the project will be to measure the binding affinity between fatty acid-conjugated bivalirudin and albumin using a state-of-the-art technique – biolayer interferometry.  She will then proceed to assess the safety of conjugates in mice by assessing whether they prevent normal clotting as well as their circulation time following injection.  If time permits, we will assess the therapeutic effects of conjugates using a model of chemical-induced thrombosis (unwanted clotting) in the carotid artery of mice.  For all outcomes, she will assess whether there are significant correlations between fatty acid size and outcomes (potency, affinity, blood loss, half-life, etc.).” 

Denise Tran, University of California, San Diego
Underrepresented Minority Gateway to Research Award

Mentor: Dr. Conor Caffrey

Research Title: The Proteasome as a Drug Target for Treatment of Schistosomiasis, a Neglected Disease of Poverty

“Schistosomiasis is a chronic ‘neglected’ disease caused by a parasitic worm that infects about 250 million of the world’s poorest people who lack access to clean water and sanitation. The parasite contaminates freshwater and invades skin to establish itself inside the blood vessels of the human host. The eggs of the worm, and the immunological reactions to them, can generate such severe pain that children cannot attend school and adults cannot work the fields or perform manual labor. Thus, schistosomiasis directly contributes to the poverty trap.

There is no vaccine for schistosomiasis, and the only treatment available is a drug called praziquantel. The drug tablet is large and has a bad taste which impedes patient compliance, especially by children. Also, praziquantel is not fully effective, meaning that worms can survive treatment and continue to make people sick. Further, if enough worms are exposed to sub-effective doses of the drug, then over time, the worry is that drug resistance might arise. More effective drugs are needed; however, because schistosomiasis is a disease of poverty, the for-profit pharmaceutical industry has little incentive to engage. Thus, academia has a key role to play in identifying and advancing new drugs, as well as new drug targets.

One promising drug target to treat parasitic infections like that caused by the schistosome is the proteasome, which is a protein complex found in all living cells and helps break down old and damaged proteins. The proteasome is essential for cell survival, and drugs that block proteasome function are already used to treat some cancers and immune diseases in humans. Although proteasomes are structurally similar between species, enough differences exist between human and parasite proteasomes to develop specific anti-parasitic drugs.

Our research Center, the Center for Discovery and Innovation in Parasitic Diseases, has already shown that anti-cancer proteasome inhibitors kill the schistosome worm by inhibiting its proteasome. Further, we recently acquired a proteasome inhibitor library from a pharmaceutical industry collaborator and found that a selection of these (‘hit compounds)’ kill the worm in culture. Based on these data, the two goals for this project are (i) assess the toxicity of the hit compounds to mammalian cells in culture, and (ii) measure their ability to biochemically inhibit the schistosome proteasome over the human proteasome anti-target. The quantitative data arising will allow us to interpret a structure-activity relationship (SAR) or profile of the specific structural elements of the hit proteasome inhibitors that are associated with decreased toxicity to mammalian cells and selectivity for the worm proteasome. This SAR, in turn, will help us plan a future chemistry campaign to synthesize more potent and selective anti-schistosome proteasome inhibitors as starting points for the development of new, and badly needed, drugs for a neglected disease of poverty.”