About

Kate Brown is the Thomas M. Siebel Distinguished Professor in History of Science at MIT. Her research explores the intersection of history, science, technology, and bio-politics, focusing on how these fields converge to create large-scale disasters and modernist wastelands. She has authored four books covering diverse topics such as population politics, linguistic mapping, nuclear weapons production and related utopian communities, the health and environmental impacts of nuclear fallout from the Chernobyl disaster, and innovations in historical narrative writing in the 21st century. Currently, she is working on a manuscript titled "Tiny Gardens Everywhere: The History of the Self-Provisioning City," which traces the role of plants and urban gardeners in 20th-century urban history, emphasizing their contributions to food sustainability, nutrient recycling, and environmental remediation in Europe and North America. Brown teaches courses in environmental history, the history of food production, the history of plants and people, and seminars on narrating the Anthropocene, with a focus on creative non-fiction narrative modes in her graduate seminars. Brown's scholarship has been widely recognized with numerous prestigious awards. Her book "A Biography of No Place: From Ethnic Borderland to Soviet Heartland" won the American Historical Association's George Louis Beer Prize for the best book in international European history. "Plutopia: Nuclear Families in Atomic Cities and the Great Soviet and American Plutonium Disasters" received multiple honors including the Albert J. Beveridge and John H. Dunning Prizes for best book in American history, the George Perkins Marsh Prize, the Ellis W. Hawley Prize, the Wayne S. Vucinich Book Prize, and the Robert G. Athearn Prize. Both of these books also earned her the Heldt Prize from the Association for Women in Slavic Studies. Her book "Dispatches from Dystopia: Histories of Places Not Yet Forgotten" was selected for Atlantic Monthly's "Best Books We Read in 2016" list. In 2015, she received the University of Maryland Regent's Award for Excellence in Research, and in 2017, she was awarded the Berlin Prize by the American Academy in Berlin. Her books have been translated into multiple languages including East European languages, Chinese, Japanese, and French. Her 2019 book "Manual for Survival" was a finalist for the National Book Critics Circle Award and the Ryszard Kapuscinski International Award for Literary Reporting. Brown has held fellowships from prestigious institutions such as the Guggenheim Foundation, the Carnegie Foundation, the European University Institute, the Kennan Institute, Harvard's Davis Center for Russian and Eurasian Studies, and the U.S. Holocaust Museum. Her research has been supported by the National Endowment for the Humanities, the American Council of Learned Societies, the International Research and Exchanges Board, and the Social Science Research Foundation. She serves as a consulting editor for the American Historical Review and co-founded its special section "History Unclassified." Her recent articles include "The Pandemic is Not a Natural Disaster" in The New Yorker and "The Little Gardens that Underwrote Soviet Globalism" in the American Historical Review. More information about her research and upcoming book can be found on her personal website and publisher's site.

Research topics

• Computer Science
• Quantum mechanics
• Physics
• Algorithm
• Theoretical computer science
• Computational science
• Distributed computing
• Engineering
• Software engineering
• Engineering physics
• Data science
• Applied mathematics
• Computer architecture
• Mathematics
• Electrical engineering
• Statistical physics
• History
• Library science
• Computer network
• Systems engineering

Selected publications

• Global Proteomics Investigation of SAMT-247 Targets: An Antiviral Thioester that Acetylates Zinc Finger Proteins

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-30

  articleOpen access

  Covalent modification of target proteins is a well-established mechanism of action for small molecule inhibitors. Cysteine residues in particular have been exploited for their reactivity toward electrophilic molecules. SAMT-247 is a mercaptobenzamide thioester that covalently acetylates cysteines in the zinc-coordinating domains of the HIV nucleocapsid protein. This SAMT-247-promoted reaction leads to loss of zinc binding by the protein, with concomitant loss of protein structure and function. Although it has low cytotoxicity in animal models, recent studies have indicated that it affects other protein targets in uninfected cells, for example leading to increased immune cell functions. In this study, global proteomics approaches have been used to better understand other protein targets of SAMT-247. Minimal effects are observed when unstimulated THP-1 monocyte cells were treated with SAMT-247. In contrast, thermal proteome profiling identified 170 proteins with altered thermal stability when THP-1 cells were stimulated with phorbol 12-myristate 13-acetate/Ionomycin (PMA/Iono) before SAMT-247 treatment. Among the affected proteins, 81 contain a zinc-coordinating domain and/or have been shown to have a reactive cysteine residue. Among these, several play a role in cellular metabolism, and Seahorse assays demonstrated that SAMT-247 significantly increased the anti-metabolic and pro-glycolytic effect of PMA/Iono in THP-1 cells. Two of the most-affected proteins were ZC3H7A, a microRNA-binding protein with four zinc finger domains, and MGMT, a DNA damage repair protein with a reactive cysteine. Both proteins were modified by SAMT-247 when tested alone or in the presence of THP-1 cell lysate, indicating that they are bona fide targets of the inhibitor. The low activity of SAMT-247 in unstimulated THP-1 cells is consistent with its low cytotoxicity. The increased effects of SAMT-247 in stimulated immune cells suggests that this molecule could be developed to target diseases other than HIV.

  PublisherDOI

• Abrogation of Oncogenic RAS Signaling by a RAS(ON) Inhibitor Doublet Primes Immune-Refractory <i>KRAS</i> <i>G12C</i> -Mutant NSCLC for Immune Checkpoint Blockade

  Cancer Discovery · 2026-02-11

  articleOpen access

  Abstract To address RAS pathway hyperactivation and targeted therapy resistance in KRASG12C-mutant non–small cell lung cancer (NSCLC), we evaluated the potential of the RAS(ON) G12C-selective covalent inhibitor elironrasib and the RAS(ON) multi-selective inhibitor daraxonrasib combination to maximize RAS pathway suppression and forestall pathway reactivation in a series of preclinical models. We demonstrate that the RAS(ON) inhibitor doublet induces profound and sustained tumor regressions and overcomes the increased RAS pathway oncogenic flux that underlies resistance to inactive state–selective KRASG12C inhibitors in NSCLC. Additionally, in immune-competent preclinical models, the RAS(ON) inhibitor doublet enhances tumor immune recognition by boosting antigen presentation and remodeling the suppressive tumor microenvironment, thus promoting immune-dependent complete regressions and sensitization of an immunorefractory model to checkpoint blockade. Collectively, these findings provide a preclinical rationale for the evaluation of a targeted RAS(ON) inhibitor doublet therapy regimen in combination with immune checkpoint blockade (ICB) in patients with KRASG12C-mutant NSCLC. Significance: The combination of a RAS(ON) G12C-selective and RAS(ON) multi-selective inhibitor mitigates clinical resistance mechanisms to KRASG12C(OFF) inhibitors and enhances tumor immune recognition, overcoming ICB resistance. These preclinical findings highlight the potential for a RAS(ON) targeted therapy regimen in combination with anti–PD-(L)1 in patients with KRASG12C-mutant NSCLC.

  PublisherDOI

• PPM1D-Mediated Regulation of the DNA Damage Repair Pathway in NK Cell Development and Migration

  Journal of Human Immunity · 2025-04-25

  articleOpen access

  PPM1D is a phosphatase that regulates the DNA damage response (DDR) by dephosphorylating some of its key players, including p53 and gH2AX. Inborn errors of immunity (IEI) with altered DDR have been associated with natural killer (NK) cell deficiency, including helicase deficiencies with increased p53 and gH2AX phosphorylation after activation. We evaluated two patients with a syndromic IEI caused by biallelic loss of function of PPM1D with B and NK cell deficiency. Besides the reduction in peripheral blood NK cell number and frequency, the patients also showed increased immature NK cells (CD56+CD62L+) and decreased mature NK cells (CD56+CD57+), while degranulation function was preserved. To investigate the role of PPM1D in NK cell maturation, we evaluated NK cell development from induced pluripotent cells in the presence of a PPM1D inhibitor (PPM1Di). PPM1Di led to a significant decrease in viability during the first stages of development and premature NK cell differentiation, followed by a reduction in NK cell frequency at endpoint, particularly impacting terminally mature NK cells. NK cell evaluation in Ppm1d-KO mice revealed an accumulation of mature NK cells in the bone marrow relative to progenitor cells. This abnormal NK cell distribution also included conserved NK cell numbers in the spleen with decreased expression of maturation markers and a relative reduction of NK cells in the blood. Analysis of healthy control human tonsil and blood NK cell subset bulk transcriptomics (GSE169646) showed higher expression of PPM1D in peripheral blood NK cell subsets compared with equivalent tonsil maturation stages, altogether indicating the relevance of PPM1D for NK cell tissue distribution and homeostasis.

  PublisherDOI

• 1990P RAS-precision medicine (RAS-PM) trans-atlantic partnership: Focus on the characteristics and outcomes of advanced KRAS-G12D non-small cell lung cancer patients

  Annals of Oncology · 2025-09-01

  article
  PublisherDOI

• C1Q+ TPP1+ macrophages promote colon cancer progression through SETD8-driven p53 methylation

  Molecular Cancer · 2025-03-31 · 16 citations

  articleOpen access

  In many tumors, the tumor suppressor TP53 is not mutated, but functionally inactivated. However, mechanisms underlying p53 functional inactivation remain poorly understood. SETD8 is the sole enzyme known to mono-methylate p53 on lysine 382 (p53K382me1), resulting in the inhibition of its pro-apoptotic and growth-arresting functions. We analyzed SETD8 and p53K382me1 expression in clinical colorectal cancer (CRC) and inflammatory bowel disease (IBD) samples. Histopathological examinations, RNA sequencing, ChIP assay and preclinical in vivo CRC models, were used to assess the functional role of p53 inactivation in tumor cells and immune cell infiltration. By integrating bulk RNAseq and scRNAseq approaches in CRC patients, SETD8-mediated p53 regulation resulted the most significantly enriched pathway. p53K382me1 expression was confined to colorectal cancer stem cells (CR-CSCs) and C1Q+ TPP1+ tumor-associated macrophages (TAMs) in CRC patient tissues, with high levels predicting decreased survival probability. TAMs promote p53 functional inactivation in CR-CSCs through IL-6 and MCP-1 secretion and increased levels of CEBPD, which directly binds SETD8 promoter thus enhancing its transcription. The direct binding of C1Q present on macrophages and C1Q receptor (C1QR) present on cancer stem cells mediates the cross-talk between the two cell compartments. As monotherapy, SETD8 genetic and pharmacological (UNC0379) inhibition affects the tumor growth and metastasis formation in CRC mouse avatars, with enhanced effects observed when combined with IL-6 receptor targeting. These findings suggest that p53K382me1 may be an early step in tumor initiation, especially in inflammation-induced CRC, and could serve as a functional biomarker and therapeutic target in adjuvant setting for advanced CRCs.

  PublisherOA PDFDOI

• 204P: Localised non-small cell lung cancer: Patient characteristics and radical radiotherapy outcomes according to KRAS mutation status

  Journal of Thoracic Oncology · 2025-03-01

  articleOpen access
  PublisherOA PDFDOI

• 1992P Targeting KRAS codon 13 mutations using combinations with RMC-8839, a novel RAS(ON) G13C-selective, tri-complex inhibitor, in non-small cell lung cancer

  Annals of Oncology · 2025-09-01 · 1 citations

  article
  PublisherDOI

• 211 Biallelic null mutations in PPM1D cause a novel combined immunodeficiency with severe neurodevelopmental defects

  Clinical Immunology · 2024-04-23

  article
  PublisherDOI

• The potential importance of the built-environment microbiome and its impact on human health

  Proceedings of the National Academy of Sciences · 2024 · 45 citations

  • Computer Science
  • Sociology
  • Biology

  There is increasing evidence that interactions between microbes and their hosts not only play a role in determining health and disease but also in emotions, thought, and behavior. Built environments greatly influence microbiome exposures because of their built-in highly specific microbiomes coproduced with myriad metaorganisms including humans, pets, plants, rodents, and insects. Seemingly static built structures host complex ecologies of microorganisms that are only starting to be mapped. These microbial ecologies of built environments are directly and interdependently affected by social, spatial, and technological norms. Advances in technology have made these organisms visible and forced the scientific community and architects to rethink gene-environment and microbe interactions respectively. Thus, built environment design must consider the microbiome, and research involving host-microbiome interaction must consider the built-environment. This paradigm shift becomes increasingly important as evidence grows that contemporary built environments are steadily reducing the microbial diversity essential for human health, well-being, and resilience while accelerating the symptoms of human chronic diseases including environmental allergies, and other more life-altering diseases. New models of design are required to balance maximizing exposure to microbial diversity while minimizing exposure to human-associated diseases. Sustained trans-disciplinary research across time (evolutionary, historical, and generational) and space (cultural and geographical) is needed to develop experimental design protocols that address multigenerational multispecies health and health equity in built environments.

  PublisherOA PDFDOI

• Targeting mutant p53-R248W reactivates WT p53 function and alters the onco-metabolic profile

  Frontiers in Oncology · 2023-01-11 · 5 citations

  articleOpen access1st authorCorresponding

  mutations. Identified from a screen, the NSC59984 compound has been shown to restore activity to mutant p53 in colorectal cancer cells. Here, we investigated its effects on esophageal adenocarcinoma cells with specific p53 hot-spot mutations. NSC59984 treatment of cells reactivated p53 transcriptional regulation, inducing mitochondrial intrinsic apoptosis. Analysis of its effects on cellular metabolism demonstrated increased utilization of the pentose phosphate pathway and inhibition of glycolysis at the fructose-1,6-bisphosphate to fructose 6-phosphate junction. Furthermore, treatment of cells with NSC59984 increased reactive oxygen species production and decreased glutathione levels; these effects were enhanced by the addition of buthionine sulfoximine and inhibited by N-acetyl cysteine. We found that the effects of NSC59984 were substantially greater in cells harboring the p53 R248W mutation. Overall, these findings demonstrate p53-dependent effects of NSC59984 on cellular metabolism, with increased activity in cells harboring the p53 R248W mutation. This research highlights the importance of defining the mutational status of a particular cancer to create a patient-centric strategy for the treatment of p53-driven cancers.

  PublisherOA PDFDOI

Recent grants

• Laser Cooling of Molecular Ions

  NSF · $454k · 2014–2018

• Collaborative Research: EPiQC: Enabling Practical-Scale Quantum Computation

  NSF · $200k · 2018–2018

• MRI: Development of a Programmable Ion-Trap Quantum Computer

  NSF · $1.1M · 2018–2023

• Collaborative Research: EPiQC: Enabling Practical-Scale Quantum Computation

  NSF · $1.0M · 2018–2024

• PFCQC: STAQ: Software-Tailored Architecture for Quantum co-design

  NSF · $15.8M · 2018–2024

Frequent coauthors

• William E. Struble

  United States Military Academy

  49 shared

• Ralph R. Landes

  Northwestern University

  49 shared

• Lloyd H. Harrison

  Eastern Virginia Medical School

  49 shared

• Michael Hesney

  Bristol-Myers Squibb (Germany)

  49 shared

• Michael L. Corrado

  49 shared

• Robert H.K. Eng

  VA New Jersey Health Care System

  49 shared

• John B. Ryan

  University of the Sciences

  49 shared

• Jason M. Amini

  40 shared

Education

• PhD, Genetics, Evolution and Environment

  University College London

  2016

• BSc Medical Genetics (year in industry), Biological Sciences

  University of Leicester

  2011