About

Michelle Brown is an associate professor of anthropology at the University of Minnesota, with a research emphasis in primate behavioral ecology. She is a biological anthropologist who studies feeding competition at multiple scales to determine how these forces shape energetics and the evolution of social relationships among primates. As the Director of the Ngogo Monkey Project, she leads a research team based in Kibale National Park in western Uganda, where they observe multiple social groups of five primate species and utilize biomarkers to track health, stress, and reproductive patterns. Her educational background includes a PhD and MA in Evolutionary Primatology from Columbia University and a BA in Cognitive Neuroscience from Harvard University. Her research contributions include studies on range utilization, intergroup conflicts, population growth constraints, dominance styles, and social and spatial relationships among primates, with publications in reputable journals such as Behavioral Ecology and Sociobiology, Philosophical Transactions of the Royal Society B, and American Journal of Primatology.

Research topics

• Computer Science
• Chemistry
• Biophysics
• Combinatorial chemistry
• Biology
• Organic chemistry
• Biochemistry
• Materials science
• Polymer chemistry
• Nanotechnology

Selected publications

• Remodeling the sarcoma microenvironment by simultaneous targeting of urokinase-type plasminogen activator receptors and epidermal growth factor receptors to promote antitumor activity

  Journal of Pharmacology and Experimental Therapeutics · 2025-08-18

  articleOpen access
  PublisherOA PDFDOI

• Exploring the Effects of Phospholipase A2 Inhibition on Brain Metabolism and Pathology in a Rat Model of Alzheimer’s Disease

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2024-11-26

  article

  Motivation: Current AD treatments do not improve cognitive deficits. Gaining a deeper understanding of the mechanisms underlying AD may reveal new therapeutic targets. Goal(s): Previous work demonstrated elevated choline levels in a preclinical model which may implicate the PLA2 pathway in AD. We aim to explore the role of PLA2 in AD. Approach: To understand the role of PLA2 in AD, we pharmacologically inhibited PLA2 in a preclinical model of AD. Metabolic, behavioural, and pathological aspects of AD were then explored using MRS, Barnes maze, immunostaining, and RNA sequencing. Results: Preliminary data indicate PLA2 inhibition reduces choline levels and improves long-term memory formation. Impact: This work may reveal PLA2 as new therapeutic target that improves cognitive deficits in Alzheimer’s disease. By linking behaviour, pathology, and metabolic processes, this study will give a well-rounded picture of how PLA2 activity impacts AD progression.

  PublisherDOI

• Understanding gaps in early detection of and rapid response to invasive species in the United States: A literature review and bibliometric analysis

  Ecological Informatics · 2024-10-24 · 7 citations

  reviewOpen access

  While concepts regarding invasive species establishment patterns and eradication possibilities have long been a topic of invasion biology, the specific terminology referring to early detection of and rapid response to (EDRR) invasive species emerged in scientific literature during the early 2000s. Since then, the EDRR approach has expanded to include a suite of detection, planning, and management tools. By conducting a systematic literature review, we attempt to characterize the field of EDRR in the United States and its territories as reflected by publication records. Specifically, we assessed publication data such as the number of publications per year, the most common journals where papers were published, and the relationship between author's keywords for studies focusing on aquatic and terrestrial habitats. For publications that used invasive species occurrence or abundance data (whether collected for the purposes of the respective publication or acquired from another data source), we manually vetted additional information such as focal taxa, data collection years and locations, sources of other data used, and whether data or code were deposited in open access formats. We also conducted network analyses for the author institutions that coauthored papers together most frequently and for the references most cited by EDRR publications. Overall, we found that silos existed in terms of which author institutions worked together, which existing literature was cited, and which topics were frequently explored. We also found evidence of substantial gaps in data access and use. For example, although a wide variety of data sources for invasive species occurrences are available, these sources were seldom cited by published literature, and newly collected data were not often deposited into invasive species databases or other open-source data repositories. Considering the continued advocation for a centralized national EDRR information system, our study indicates that facilitating access to data, decision support tools, and other informational resources represents a key opportunity for improving EDRR capabilities.

  PublisherDOI

• Enhancing pDNA Delivery with Hydroquinine Polymers by Modulating Structure and Composition

  JACS Au · 2023-06-28 · 12 citations

  articleOpen access

  Quinine is a promising natural product building block for polymer-based nucleic acid delivery vehicles as its structure enables DNA binding through both intercalation and electrostatic interactions. However, studies exploring the potential of quinine-based polymers for nucleic acid delivery applications (transfection) are limited. In this work, we used a hydroquinine-functionalized monomer, HQ, with 2-hydroxyethyl acrylate to create a family of seven polymers (HQ-X, X = mole percentage of HQ), with mole percentages of HQ ranging from 12 to 100%. We developed a flow cytometer-based assay for studying the polymer-pDNA complexes (polyplex particles) directly and demonstrate that polymer composition and monomer structure influence polyplex characteristics such as the pDNA loading and the extent of adsorption of serum proteins on polyplex particles. Biological delivery experiments revealed that maximum transgene expression, outperforming commercial controls, was achieved with HQ-25 and HQ-35 as these two variants sustained gene expression over 96 h. HQ-44, HQ-60, and HQ-100 were not successful in inducing transgene expression, despite being able to deliver pDNA into the cells, highlighting that the release of pDNA is likely the bottleneck in transfection for polymers with higher HQ content. Using confocal imaging, we quantified the extent of colocalization between pDNA and lysosomes, proving the remarkable endosomal escape capabilities of the HQ-X polymers. Overall, this study demonstrates the advantages of HQ-X polymers as well as provides guiding principles for improving the monomer structure and polymer composition, supporting the development of the next generation of polymer-based nucleic acid delivery vehicles harnessing the power of natural products.

  PublisherOA PDFDOI

• Cinchona Alkaloid Polymers Demonstrate Highly Efficient Gene Delivery Dependent on Stereochemistry, Methoxy Substitution, and Length

  Biomacromolecules · 2023-12-27 · 6 citations

  article

  Nucleic acid delivery with cationic polymers is a promising alternative to expensive viral-based methods; however, it often suffers from a lower performance. Herein, we present a highly efficient delivery system based on cinchona alkaloid natural products copolymerized with 2-hydroxyethyl acrylate. Cinchona alkaloids are an attractive monomer class for gene delivery applications, given their ability to bind to DNA via both electrostatics and intercalation. To uncover the structure-activity profile of the system, four structurally similar cinchona alkaloids were incorporated into polymers: quinine, quinidine, cinchonine, and cinchonidine. These polymers differed in the chain length, the presence or absence of a pendant methoxy group, and stereochemistry, all of which were found to alter gene delivery performance and the ways in which the polymers overcome biological barriers to transfection. Longer polymers that contained the methoxy-bearing cinchona alkaloids (i.e., quinine and quinidine) were found to have the best performance. These polymers exhibited the tightest DNA binding, largest and most abundant DNA-polymer complexes, and best endosomal escape thanks to their increased buffering capacity and closest nuclear proximity of the payload. Overall, this work highlights the remarkable efficiency of polymer systems that incorporate cinchona alkaloid natural products while demonstrating the profound impact that small structural changes can have on overcoming biological hurdles associated with gene delivery.

  PublisherDOI

• 3D cell-culture strategy for screening novel agents in Fanconi Anemia chemoprevention

  2023-09-28

  preprintOpen access

  Fanconi anemia (FA) patients have DNA repair mutations predisposing them to oral cancers so treatment with non-DNA damaging agents is highly desired. As cancer experimental therapeutics advance towards study paradigms that more carefully mimic physiology, e.g. organoids and spheroids. Presently, we are using a 3D cell culture method emphasizing layers of extracellular matrix (ECM) as FA premalignant lesions retain epithelial architecture. We conducted 3D screening studies using 2 layered geometries: 1) nanofibers coated with 1 ng/mL 2:1 Collagen III/IV (C3C4) then 100 pg/mL 2.75:1 Tenascin C/Fibronectin (TNFN) and 2) polystyrene layered with 50 ug/mL C3C4 then 3.5 ug/mL TNFN. We developed these coatings to maximize lipid raft recovery, a drug transport feature lost in 2D culture. The ECM impact on FA cell drug transport was characterized by comparing effective nuclear delivery of a 20nm nanoencapsulated FITC-labeled RNAi compound (s50-TBG-RNAi3UTR), known to require lipid rafts, to the same oligo formulated with Dotap in a FA HNSCC cell line (FA1). Using confocal microscopy and IMARS software to segment delivery at maximal nuclear intensity into nuclear or endolysosomal compartments, we found, for FA1 cells on ECM, nuclear oligo signal colocalization with nuclear compartment ± coefficient of variation was 62 ± 2.2% for the capsule vs 9.8 ± 8.5% for Dotap oligo. On glass, nuclear delivery was 10 ± 52% for s50 capsule vs 25 ± 32% for Dotap. Endolysosomal compartment sequestration was respectively 28 ± 12, 62 ± 10, 44 ± 19 and 51 ± 15%. This illustrates a relevant decrease in variation in FA cell biology from ECM addition. Next, we studied metformin (Met) and pioglitazone (Pio)(agents in current oral cancer prevention studies) combined with G2/M blockade inhibitors, MK1775 (Wee1 kinase inhibitor) and GSK461364 (PLK inhibitor) in FA1s. Inhibiting G2/M blockade, already induced by FA-derived DNA damage, could promote inappropriate cell division, mitotic catastrophe (MTOC) and death. In initial 2D FA1 growth studies, increased death was observed with Met plus MK1775. 3D studies, in contrast, showed increased cell death for FA1s treated with Pio plus either MK1775 or s50-TBG-RNAiCK2 (RNAiCK2). Confocal mechanistic studies in cells plated on ECM and treated for 18 hours, indicated Pio + MK1775 had inhibited Survivin and ß-catenin upregulation and FA1 cells did proceed into MOC and death. For Pio (PPARg agonist) + RNAiCK2, RXRa was dephosphorylated at S260, enabling its escape from cytosolic sequestration to bind nuclear PPARg, initiating differentiation. Differentiation was indicated by upregulation of panKeratin and Transglutaminase-3. We conclude combination therapies with high interest agents in FA-associated oral cancer can be performed in 3D culture systems and might confirm drug mechanisms of action, thus augmenting other standard methods of cancer drug evaluation and screening (e.g. cell proliferation and clonogenicity).

  PublisherOA PDFDOI

• Abstract 5272: 3D cell-culture strategy for screening novel agents in Fanconi anemia chemoprevention

  Cancer Research · 2023-04-04

  article

  Abstract Fanconi anemia (FA) patients have DNA repair mutations predisposing them to oral cancers so treatment with non-DNA damaging agents is highly desired. As cancer experimental therapeutics advance towards study paradigms that more carefully mimic physiology, e.g. organoids and spheroids. Presently, we are using a 3D cell culture method emphasizing layers of extracellular matrix (ECM) as FA premalignant lesions retain epithelial architecture. We conducted 3D screening studies using 2 layered geometries: 1) nanofibers coated with 1 ng/mL 2:1 Collagen III/IV (C3C4) then 100 pg/mL 2.75:1 Tenascin C/Fibronectin (TNFN) and 2) polystyrene layered with 50 ug/mL C3C4 then 3.5 ug/mL TNFN. We developed these coatings to maximize lipid raft recovery, a drug transport feature lost in 2D culture. The ECM impact on FA cell drug transport was characterized by comparing effective nuclear delivery of a 20nm nanoencapsulated FITC-labeled RNAi compound (s50-TBG-RNAi3UTR), known to require lipid rafts, to the same oligo formulated with Dotap in a FA HNSCC cell line (FA1). Using confocal microscopy and IMARS software to segment delivery at maximal nuclear intensity into nuclear or endolysosomal compartments, we found, for FA1 cells on ECM, nuclear oligo signal colocalization with nuclear compartment ± coefficient of variation was 62 ± 2.2% for the capsule vs 9.8 ± 8.5% for Dotap oligo. On glass, nuclear delivery was 10 ± 52% for s50 capsule vs 25 ± 32% for Dotap. Endolysosomal compartment sequestration was respectively 28 ± 12, 62 ± 10, 44 ± 19 and 51 ± 15%. This illustrates a relevant decrease in variation in FA cell biology from ECM addition. Next, we studied metformin (Met) and pioglitazone (Pio)(agents in current oral cancer prevention studies) combined with G2/M blockade inhibitors, MK1775 (Wee1 kinase inhibitor) and GSK461364 (PLK inhibitor) in FA1s. Inhibiting G2/M blockade, already induced by FA-derived DNA damage, could promote inappropriate cell division, mitotic catastrophe (MOC) and death. In initial 2D FA1 growth studies, increased death was observed with Met plus MK1775. 3D studies, in contrast, showed increased cell death for FA1s treated with Pio plus either MK1775 or s50-TBG-RNAiCK2 (RNAiCK2). Confocal mechanistic studies in cells plated on ECM and treated for 18 hours, indicated Pio + MK1775 inhibited Survivin and ß-catenin upregulation and FA1 cells did proceed into MOC and death. For Pio (PPARg agonist) + RNAiCK2, RXRa was dephosphorylated at S260, enabling its escape from cytosolic sequestration to bind nuclear PPARg, initiating differentiation. Differentiation was indicated by upregulation panKeratin and Transglutaminase-3. We conclude combination therapies with high interest agents in FA-associated oral cancer can be performed in 3D culture systems and might confirm drug mechanisms of action, thus augmenting other standard methods of cancer drug evaluation and screening (e.g. cell proliferation and clonogenicity). Citation Format: Gretchen M. Unger, Beverly R. Wuertz, Mary E. Brown, Sanjana Arji, Janeen H. Trembley, Frank G. Ondrey. 3D cell-culture strategy for screening novel agents in Fanconi anemia chemoprevention. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5272.

  PublisherDOI

• MET Receptor Tyrosine Kinase Inhibition Reduces Interferon-Gamma (IFN-γ)-Stimulated PD-L1 Expression through the STAT3 Pathway in Melanoma Cells

  Cancers · 2023-06-29 · 8 citations

  articleOpen access

  Melanoma is the leading cause of death from cutaneous malignancy. While targeted therapy and immunotherapy with checkpoint inhibitors have significantly decreased the mortality rate of this disease, advanced melanoma remains a therapeutic challenge. Here, we confirmed that interferon-gamma (IFN-γ)-induced PD-L1 expression in melanoma cell lines. This increased expression was down-regulated by the reduction in phosphorylated STAT3 signaling via MET tyrosine kinase inhibitor treatment. Furthermore, immunoprecipitation and confocal immunofluorescence microscopy analysis reveals MET and PD-L1 protein-protein interaction and colocalization on the cell surface membrane of melanoma cells. Together, these findings demonstrate that the IFN-γ-induced PD-L1 expression in melanoma cells is negatively regulated by MET inhibition through the JAK/STAT3 signaling pathway and establish the colocalization and interaction between an RTK and a checkpoint protein in melanoma cells.

  PublisherOA PDFDOI

• Combinatorial Polycation Synthesis and Causal Machine Learning Reveal Divergent Polymer Design Rules for Effective pDNA and Ribonucleoprotein Delivery

  JACS Au · 2022-02-07 · 63 citations

  articleOpen access

  hydrophobic interactions. These payload-specific design guidelines will inform further design of bespoke polymers for specific therapeutic contexts.

  PublisherDOI

• A cortactin CTTN coding SNP contributes to lung vascular permeability and inflammatory disease severity in African descent subjects

  Translational research · 2022-02-15 · 8 citations

  articleOpen access
  PublisherOA PDFDOI

Frequent coauthors

• JoAnne McLaurin

  Sunnybrook Health Science Centre

  65 shared

• Theresa M. Reineke

  University of Minnesota System

  38 shared

• Bojana Stefanovic

  Sunnybrook Research Institute

  32 shared

• Zhe Tan

  University of Minnesota

  28 shared

• Shan Jiang

  26 shared

• Ngoc Le

  Vietnam National University Ho Chi Minh City

  26 shared

• Isabelle Aubert

  Sunnybrook Research Institute

  25 shared

• Steven M. Dudek

  University of Illinois Chicago

  24 shared

Labs

• Ngogo Monkeys LabPI