Denis Ohlstrom
BME PhD Proposal Presentation
Date: 2025-10-09
Time: 3:00 - 5:00 PM
Location / Meeting Link: Health and Science Research Building 2, Room 357.
Committee Members:
Dr. Manoj Bhasin; Dr. Holly Bauser-Heaton; Dr. Melissa Kemp; Dr. Wilbur Lam; Dr. Daniel Sherbenou
Title: Longitudinal evaluation of high-risk hematologic malignancies and the immune microenvironment at single cell and spatial resolution
Abstract:
Hematologic malignancies are a major cause of cancer-related morbidity and mortality, accounting for approximately 40% of childhood cancers and 10% of adult cancers in the United States. Advances in pre-treatment risk stratification using clinical features, genetics, and transcriptomics have improved the ability to personalize therapy; however, current models remain imperfect and often fail to fully capture patient risk. Incorporating emerging features such as malignant cell heterogeneity, immune system dysfunction, and the spatial organization of the bone marrow microenvironment may provide insights into disease mechanisms and enable more precise risk stratification. Importantly, the evolution of these features across the disease course remains poorly understood. This project seeks to define the dynamics of malignant and immune cell populations from disease diagnosis to post-treatment remission and eventual disease relapse. Using a longitudinal, multi-omic framework that integrates single-cell RNA sequencing, whole genome sequencing, bulk RNA sequencing, and spatial transcriptomics, the proposed research will address three primary aims: (Aim 1) Identify treatment-resistant subtypes of pediatric acute myeloid leukemia and uncover targetable therapeutic vulnerabilities. (Aim 2) Characterize the dynamic interplay between malignant cells and immune dysfunction across the multiple myeloma disease course. (Aim 3) Map spatially resolved tumor-immune interactions at diagnosis and disease relapse to reveal mechanisms of immune escape in multiple myeloma. Together, these studies will generate a detailed depiction of malignant and immune cell states, reveal biomarkers of treatment response, and highlight actionable targets for drug repurposing, ultimately advancing precision therapy and risk prediction in hematologic malignancies.
