Congratulations to the Year 5 BDCI Accelerator Grant Recipients!
We are thrilled to announce the recipients of the Year 5 BDCI Accelerator Grants! These grants aim to further cultivate the network of Emory researchers working at the critical intersection of chemistry, biology, and human health, and fund innovative, cross-disciplinary projects that align with the mission of the BDCI.
This year’s proposals span three major units at Emory, five individual departments, multiple therapeutic areas, and a diverse set of technological approaches. These six groups will receive $40,000 over the next year to complete the aims outlined in their proposal, with the ultimate goal of providing the preliminary data necessary to apply for larger, extramural funding. The 2024 projects — along with their investigators — that received Accelerator Grants are:
Tyler Beyett + Simon Blakey: New chemical strategies for the design of EGFR kinase inhibitors
Mutations in the Epidermal Growth Factor Receptor gene (EGFR) are common causes of lung cancer, which is especially prevalent in the US Southeast. Although there are several EGFR inhibitors on the market, patients often develop resistance, necessitating the development of EGFR therapeutics with new mechanisms of action. The proposed work will explore how new reactive groups can be incorporated into existing EGFR kinase inhibitors to enhance their pharmacological properties, thus improving patient outcomes. The project has emerged from a new collaboration at Emory between Tyler Beyett, a newly established Assistant Professor in Pharmacology & Chemical Biology, and Simon Blakey, a well-established Professor in Chemistry, and will expand upon their respective expertise in structure-based drug design and synthetic chemistry.
“We are excited to receive support from BDCI on our project and establish a new collaboration on a project that fits with the mission of BDCI – to apply innovative chemistry methods to discover new biology.”
Fikri Birey + Khalid Salaita: Investigating mechano-regulation of human brain development through neuronal migration with tunable, genetically encoded tension sensors
Consider the following question: How do migrating neurons use mechanical forces to sculpt the intricate architecture of the brain? The importance of this question lies in the fact that changes in the mechanical properties of neurons and the brain matrix are associated with multiple diseases, including congenital birth defects, autism spectrum disorders, schizophrenia, and even Alzheimer’s disease. Fikri Birey (Human Genetics) and Khalid Salaita (Chemistry) have formed a new collaboration to tackle this important question, combining their unique expertise in protein engineering, mechanobiology, and neurodevelopment. As they point out, very little is known about how forces instruct developmental phenomena at the single cell level, leaving this team with many exciting opportunities for discovery in this critical area of human development!
“We are thrilled to be able to push the frontier of interdisciplinary science to cover completely new territory with the support of the BDCI! This seed award presents us with a unique chance to bridge disciplinary divides between our respective domains of investigation, chemistry, and neurobiology, paving the way to explore and reveal aspects of biology that were once beyond our reach.”
Mingji Dai + Yong Wan: Targeting PRMT5–MEP50 PPI with novel small molecules for therapeutic development
Targeting challenging protein-protein interactions is a grand challenge in the discovery of new therapeutics for many diseases, including breast cancer. Triple negative breast cancer (TNBC) is an aggressive disease with limited treatment options and frequent resistance, and is therefore a high-priority area for novel therapeutic development. This project aims to develop inhibitors that target the interface between protein arginine methyl transferase 5 (PRMT5), a post-translational modifying enzyme with a well-established role in breast cancer, and a key adaptor protein. Successful targeting of the PRMT5-adaptor protein interaction would not only provide a new therapeutic strategy for TNBC, but also address an important unmet medical need. Mingji Dai (Chemistry) and Yong Wan (Pharmacology & Chemical Biology) have teamed up to integrate their expertise in medicinal chemistry and cancer biology to target this challenging, but critical protein-protein interface.
“We’re excited to receive this award, which will allow us to initiate this exciting collaboration to obtain critical results for external funding applications!”
Sohail Khoshnevis + Yuhong Du: Targeting translation machinery in Candida albicans to combat infection
Fungal infections are responsible for an estimated 1.5 million deaths per year. The current treatments for fungal infections are mostly restricted to polyenes, azoles, and echinocandins, which target fungal cell walls and membranes. Use of these antifungals is limited by their toxicity, drug-drug interactions, and the emergence of resistance, which poses a risk to the healthcare system and underscores the importance of identifying novel therapeutic targets and new treatment approaches. This project aims to discover potent compounds that target the translational machinery in Candida albicans, thus identifying a novel mechanism of action to address the above issues related to current anti-fungal therapeutics. The combination of Sohail Khoshnevis’ (Biochemistry) expertise in RNA and protein biochemistry and fungal biology and Yuhong Du’s (Emory Chemical Biology Discovery Center) expertise in drug screening and chemical biology creates a unique opportunity for this group to advance the field of anti-fungal therapeutics and significantly improve the lives of patients suffering with Candida albicans infections.
The Khoshnevis lab is “thrilled to have received this Accelerator Grant, which will allow us to establish a new research area in our group!”
Tom Kukar + Yuhong Du: Therapeutic targeting of pathogenic lipid droplets in a human microglial model of neurodegeneration
Loss-of-function mutations in the progranulin gene are a major cause of frontotemporal dementia and a risk factor for Alzheimer’s and Parkinson’s disease. Although it is known that granulins help maintain normal lipid turnover in the lysosome, the reason why loss of granulins leads to neurodegeneration has been elusive. To address this, the proposed project will use high-content imaging to identify small molecules that can rescue abnormal lysosomal function and lipid droplet formation in a human microglial model of frontotemporal dementia caused by progranulin mutations. This project expands the Kukar lab’s (Pharmacology & Chemical Biology) research using iPSC-microglia cell models into the drug discovery and chemical biology space through a new collaboration with Dr. Yuhong Du, Associate Director of the Emory Chemical Biology Discovery Center. The ultimate goal of this work is to identify lead compounds to develop drugs to treat multiple neurodegenerative diseases.
“We are thrilled and honored to receive this award! These funds will allow us to combine cutting edge cell and chemical biology to help understand the function of progranulin and identify small molecules to guide therapeutic development for neurodegenerative diseases, which are desperately needed.”
Stephen Pelly + Christina Gavegnano: Selective JAK2 inhibitors optimized for CNS penetration for the treatment of HIV-associated neurocognitive disorders & a pathway to a cure for HIV
Although the progression of HIV infection to AIDS is controllable with effective antiretroviral therapy, HIV persistence in the central nervous system (CNS) leads to chronic local inflammation and subsequently neurocognitive impairment in as much as half the population living with HIV. This project aims to design novel, CNS penetrant drugs with an immunomodulatory effect as an effective treatment to reverse HIV-associated neurocognitive disorder (HAND) and therefore provide an effective treatment option for these patients. This collaboration between Steve Pelly (Liotta research group, Chemistry) and Christina Gavegnano (Pathology & Laboratory Medicine) synergizes the Liotta group’s expertise in rational design and synthesis of small molecule receptor agonists with the Gavegnano lab’s biological systems in which to evaluate these compounds, thereby forming a drug discovery team with all the necessary skills and infrastructure to be effective in this endeavor.
“Drug discovery is truly a team effort, and this project brings together two highly skilled and effective teams whose roles are very different, yet indispensable for the overall success of the project. Both teams are passionate about the work and look forward to driving this project forward in the months to come!”
Please join us in congratulating our awardees! We look forward to hearing their progress and seeing what exciting breakthroughs come as a result of their work!
Applications for the next round of Accelerator Grants will open Fall 2024. Stay tuned for updates.