Andrea Patterson, Ph.D.
980 W. Walnut Street
Walther Hall, R3 322
Indianapolis, IN 46202
Phone: (317) 278-2485
Research Program Membership
Assistant Research Professor
Department of Medicine
Division of Hematology/Oncology
IU School of Medicine
Dr. Patterson's research interests include:
1. HEMATOPOIESIS AND RADIOBIOLOGY. I am interested in cellular and molecular mechanisms of radiation injury to the hematopoietic system and protection and mitigation of this injury using compounds under consideration for development as licensed medical countermeasures. I recently defined the cellular and molecular radioprotective mechanisms of dimethyl prostaglandin E2 (dmPGE2) in our murine model of the hematopoietic acute radiation syndrome (H-ARS) (Patterson et al., 2020, Stem Cell Reports), and further defined time frames of administration pre- and post-irradiation for optimal survival (Patterson et al., 2020, Radiation Research). I am PI on a NIAID/NIH U19 Centers for Medical Countermeasures against Radiation (CMCR) pilot grant (PI of the parent U19 at IU is Dr. Orschell) to further the development of dmPGE2 for treatment of H-ARS by defining mechanisms of radio-mitigation in mice. This grant will also develop a CD34-humanized NSG (huCD34-NSG) mouse H-ARS model, allowing investigation of mechanisms of radiomitigation in humanized mice, a powerful translational tool for the radiation countermeasure field. I expect the above work to advance the development pipeline of dmPGE2 and facilitate future external awards towards this effort. I also anticipate utilizing the methods I develop in hematopoietic analysis of huCD34-NSG radiation responses for additional proposals both supporting translational development of other H-ARS radiomitigators through collaborations within the CMCR Consortium and throughout the radiation/nuclear countermeasures community, and based on novel biological insights from in-depth analysis of human hematopoietic stem and progenitor cells irradiated in vivo. It is important to note that all this work has direct applicability to amelioration of off target/normal tissue effects resulting from cancer treatment. 2. BIOLOGY OF HEMATOPOIETIC AGING. I am interested in cellular and molecular mechanisms of hematopoietic aging and amelioration of aging defects. I recently established that the long-term engraftment potential of aged bone marrow grafts can be significantly increased by ex vivo dmPGE2 pulse exposure, as has been shown previously for grafts from young mice, and I identified relevant signaling pathways conserved in young and aged hematopoietic stem cells (HSCs) as likely mediators of this enhancement. This research also developed novel insights into changes in HSC responsiveness with age at the transcriptional level (Patterson et. al., 2021, Stem Cell Reviews and Reports). I plan to expand upon my identified molecular signaling pathways in aged HSCs to test novel targets for enhancement of hematopoiesis and transplantation in aged mice; molecules of interest include those involved in cell survival and homeostasis which I identified to have conserved stimulation by dmPGE2, as well as those found to have altered responsiveness with age, which can be targeted by activating and inhibitory compounds. 3. HEMATOPOIETIC AGING AND RADIATION. At the intersection of my work in hematopoietic aging and radiation, I recently contributed to the establishment of murine models of H-ARS in multiple age groups including pediatric (Patterson et al., 2021, Radiation Research) geriatric and middle-aged populations (Patterson et al., manuscript in preparation for Radiation Research), and a genetically diverse “JDO” model of young adult mice considered a more accurate representation of the human population (Patterson et al. 2020, Health Physics Journal). My work on aging radiation models includes mechanisms of increased radio-resistance with age, and sex determinants of differential hematopoietic radiosensitivity in aged males and females at the whole animal, cellular, and genomic levels. The sex-specific cellular and transcriptomic analyses of aged HSC revealed molecules of interest which may play a role in differential radiosensitivity with age and sex, and these will be explored further as potential targets for novel strategies to enhance radiation recovery. In addition, I am in the process of writing a proposal in response to a NIAID Radiation Nuclear Countermeasures Program Notice of Special Interest for “Pediatric Radiation/Nuclear Animal Models, MCM, Biodosimetry Development” for submission in November 2021, which will extend our pediatric H-ARS model into the genetically diverse JDO strain and perform MCM testing in the pediatric JDO model. Given the implications of chronic inflammation in both aging defects and late radiation injuries, I am investigating the change in cytokine profiles with age across our various H-ARS models described above (pediatric through geriatric ages, inbred and outbred mice) in both bone marrow and serum, at steady state and after radiation exposure with and without administration of PLX-R18 cells, a GMP-grade human mesenchymal stem cell product (PLX). These cells are shown to increase survival from H-ARS through real-time in vivo secretion of pro-hematopoietic soluble factors. This work will provide biological insights into the contribution of cytokine changes to both natural aging, general radiation responses with age, and radio-mitigation by PLX cells in different age groups and models of H-ARS. These findings are also likely to spark avenues of further funding for cytokine manipulation studies towards enhancement of hematopoietic aging and/or radio-mitigation strategies. As radiation exposure can lead to long-term immune dysfunction, I also plan to define the effects of age and sex on radiation-induced immune dysfunction and define novel genetic and cytokine correlates of post-irradiation immune phenotypes, utilizing the full strength of our established pediatric, adult, geriatric, and genetically diverse murine models of H-ARS and DEARE. I am currently proposing this work in a 5-year multi-PI U01 application along with Dr. Martin Richer (IUSM), who brings expertise in murine immunology and virus infection models, for submission in August 2021 to the NIAID RFA-AI-21-019 entitled “Radiation-Induced Immune Dysfunction” (https://grants.nih.gov/grants/guide/rfa-files/RFA-AI-21-019.html). Since radiation-induced cellular senescence has emerged as a causative mechanism to the delayed effects of acute radiation exposure (DEARE), we will also test the effect of senolytic agents on radiation-induced immune dysfunction with age and sex in collaboration with Dr. Daohong Zhou at the University of Florida, a leader in the development and use of senolytic agents in the DEARE. 4. HEMATOPOIETIC STEM CELL MOBILIZATION FOR TRANSPLANT. An additional research interest is enhancement of hematopoietic stem cell mobilization for transplant in hematologic oncology patients. As part of a clinical trial utilizing an NSAID (Meloxicam) to manipulate PGE2 levels in vivo during the G-CSF-mediated mobilization process, I defined gene signatures in mobilized CD34+ cells which suggest that Meloxicam may counteract oxidative stress during collection with the potential to reduce stem cell exhaustion (Patterson et. al., manuscript in preparation for Stem Cell Reviews and Reports). References: Please see attached CV for the referenced publications.
Post-doctoral Fellowship - Indaina University School of Medicine, Indianapolis, IN 12/2018
Ph.D. - University of Oklahoma Health Science Center, Oklahoma City, OK 11/2015