Convergence Institute Innovation Pilot Grants

Pilot Program

The goal of the Convergence Institute at Johns Hopkins is to bring together the brightest minds in cancer biology, clinical oncology, engineering, and computational biology to make new discoveries and bring forward the next generation of cancer therapies. The Institute consists of a transdisciplinary team of faculty and co-mentored trainees across career stages.

Innovation Pilot Grants will be funded by the Convergence Institute and will be available for use in FY23. We anticipate making two awards at $50k each.

Convergence Institute Innovation Pilot Grants

Image of Daniel Laheru
Daniel Laheru, MD
Image of Andrew Ewald
Andrew Ewald, PhD

The Convergence Institute provides an incubator for transdisciplinary research blending new technologies for biomedical research with potential clinical applications. To enable this research goal, our pilot grants program, led by Dr. Daniel Laheru and Dr. Andrew Ewald, offers researchers across the University the opportunity to form new teams inventing new technologies for cancer research and expediting their adoption for clinical practice. These pilots provide a high-risk high reward testing ground that provides the foundation to develop future large-scale team science projects that can leverage additional funding mechanisms for the Institute. Out of 12 applications to the program, two projects led by Dr. Nathaniel Brennen and Dr. Nilofer Azad were selected for awards at $50,000 each due to their innovation and impact on predictive medicine.  

Multi-Data Approach to Determine Drug Viability in Prostate Cancer

Dr. Nathaniel Brennen’s collaborative project integrates cutting edge spatial transcriptomic and proteomic technology and with clinical research to ask the question, “Does LSD1 inhibition via Bomedemstat promote anti-tumor immune responses in metastatic castration-resistant prostate cancer (mCRPC) patients?” Bomedemstat is an oral medication used to treat many types of cancer by promoting an immune response to deactivate LSD1, a protein known to drive the growth of tumor cells in certain types of cancer. This project is leveraging patient samples from an ongoing clinical trial of Bomedemstat in mCRPC patients to understand:

1) Spatially resolved infiltration of immune cells and their cellular interactions

2) The spatial distribution of drug penetration within the tumor

The spatially resolved data from this project gives an in-depth analysis of drug distribution and effects within the tumor that is more informative than bulk data information from standard analysis methods. The novel methodology in this project includes Applied Imaging Mass Spectrometry (AIMS) to determine spatially resolved drug distribution, staining and spatial imaging of 85 biological markers and proteins in a single sample using Nanostring GeoMx Deep Spatial Profiler (DSP), spatial transcriptomics analysis of gene expression, and ultimately integration of all of this data to understand changes to cellular interactions in response to Bomedemstat treatment.

Comparison of samples from patients that are known responders and non-responders this drug therapy will provide researchers with data to identify patients who will benefit from this treatment. This project will also advance the analysis platforms and data integration processes available to study other cancer drugs and their effects within the tumor.

Image of Nathaniel Brennen
Dr. Nathaniel Brennen

Immune-Profiling and Genetic Analysis of Colorectal Patient Biospecimens from a Combination Therapy Clinical Trial

Dr. Nilofer Azad, MD

Nilofer Azad, M.D. submitted an application examining if “Phosphatidylinositol 3-kinase (PI3K) inhibition with copanlisib in combination with nivolumab will enhance CD8+ T cell infiltration and activation in the tumor microenvironment (TME).” Copanlisib is a therapeutic inhibitor of the Phosphatidylinositol 3-kinase (PI3K) protein, which is part of a molecular pathway involved in tumor cell survival and proliferation. Nivolumab is an immune checkpoint inhibitor drug approved for use in patients with specific defects in DNA repair. A recent clinical trial by Dr. Azad’s team testing these two drugs together showed significant success in some patients indicating a possible synergy between the two drugs.  

Comparison of biopsy samples before and after treatment, between patient subgroups of responders and non-responders, and between patients with and without mutations in PI3K may contain valuable information on:

1) The impact of this drug combination on the immune modulation within the tumor and it’s microenvironment

2) Biomarkers that could potentially differentiate patients who may benefit the most from this treatment

Leveraging the spatial proteomics capabilities of the Convergence Institute, changes in immune cell infiltration and composition and complex cell signaling pathway analyses will be performed in collaboration with Dr. Robert Anders group. Whole exome sequencing and muti-omic multivariate analysis of acquired data will be done with the Experimental and Computational Genomics Core and with the expertise of Dr. Yegnasubramanian’s team.  These combined results will help researchers understand how these two drugs work together and spur new preclinical studies of improved combination therapies with nivolumab, copanlisib and other chemotherapeutic drugs. Avenues to directly translate technology-derived information differentiating patients that may derive the most benefit from this treatment into targeted patient clinical trials are also available.