About

Craig Steven Wilder is the Barton L. Weller Professor of History at MIT, specializing in American institutions and ideas. He is the author of the award-winning book Ebony & Ivy: Race, Slavery, and the Troubled History of America’s Universities, which explores the historical ties of American colleges and universities to slavery and the slave trade. His work has influenced public acknowledgments and research initiatives across numerous institutions, and his scholarship has inspired cultural references and media portrayals. Wilder has also authored other books examining African American culture and race relations, and has contributed essays on the history of higher education, slavery, and social power in America. He has served as a senior fellow at the Bard Prison Initiative, advising on educational programs within the prison system, and has participated in numerous documentary projects and museum exhibits related to American history, race, and social justice. Wilder has taught at several universities, including Columbia University, Dartmouth College, Williams College, and Long Island University, and has been a visiting professor at the New School University and University College London. He serves on the board of the Lapidus Center for the Historical Analysis of Transatlantic Slavery at the Schomburg Center, and has been involved in community organizing in the South Bronx, emphasizing his engagement with both academic scholarship and public history.

Research topics

• Cell biology
• Immunology
• Political Science
• Computer Science
• Biology
• Genetics
• Medicine
• Cancer research
• Physics
• Public relations
• Computational biology
• Cognitive psychology
• Neuroscience
• Psychology
• Medical education

Selected publications

• Four guiding principles for effective trainee-led STEM community engagement through high school outreach

  PLoS Computational Biology · 2023 · 6 citations

  Senior authorCorresponding
  • Political Science
  • Medical education
  • Political Science

  To address ongoing academic achievement gap, there is a need for more school-university partnerships promoting early access to STEM education. During summer 2020, members of our institute initiated QBio-EDGE (Quantitative Biology-Empowering Diversity and Growth in Education), an outreach program for high schools in Los Angeles. In the hope of contributing to increasing diversity in academia, QBio-EDGE aims to make STEM education more accessible for students from historically excluded communities by exposing them to scientific research and diverse scientist role models. This program is led by early career researchers (ECRs), i.e., undergraduate, graduate, and postdoctoral researchers. In our first year, the outreach activities took place during virtual learning, presenting challenges and opportunities within the program development. Here, we provide a practical guide outlining our outreach efforts, key factors we considered in the program development, and hurdles we overcame. Specifically, we describe how we assembled our diverse team, how we established trusting partnerships with participating schools, and how we designed engaging student-centered, problem-based classroom modules on quantitative biology and computational methods applications to understand living systems. We also discuss the importance of increased institutional support. We hope that this may inspire researchers at all career stages to engage with local schools by participating in science outreach, specifically in quantitative and computational fields. We challenge institutions to actively strengthen these efforts.

  PublisherOA PDFDOI

• A stimulus‐contingent positive feedback loop enables IFN‐β dose‐dependent activation of pro‐inflammatory genes

  Molecular Systems Biology · 2023 · 14 citations

  1st authorCorresponding
  • Computer Science
  • Biology
  • Cell biology

  Type I interferons (IFN) induce powerful antiviral and innate immune responses via the transcription factor, IFN-stimulated gene factor (ISGF3). However, in some pathological contexts, type I IFNs are responsible for exacerbating inflammation. Here, we show that a high dose of IFN-β also activates an inflammatory gene expression program in contrast to IFN-λ3, a type III IFN, which elicits only the common antiviral gene program. We show that the inflammatory gene program depends on a second, potentiated phase in ISGF3 activation. Iterating between mathematical modeling and experimental analysis, we show that the ISGF3 activation network may engage a positive feedback loop with its subunits IRF9 and STAT2. This network motif mediates stimulus-specific ISGF3 dynamics that are dependent on ligand, dose, and duration of exposure, and when engaged activates the inflammatory gene expression program. Our results reveal a previously underappreciated dynamical control of the JAK-STAT/IRF signaling network that may produce distinct biological responses and suggest that studies of type I IFN dysregulation, and in turn therapeutic remedies, may focus on feedback regulators within it.

  PublisherOA PDFDOI

• Four guiding principles for effective trainee-led STEM community engagement through high school outreach

  2022-03-31

  preprintOpen accessSenior authorCorresponding

  The education system in the US displays troubling disparities in academic performance of different racial and income groups, known as the achievement gap. During summer 2020, our research group committed to promoting racial and ethnic diversity in academia to reduce the achievement gap in Los Angeles. Since educators with a growth mindset employing active learning in their classrooms can elevate performance of students from underrepresented minority groups in STEM fields, we initiated QBio-EDGE (Quantitative Biology - Empowering Diversity and Growth in Education), a trainee-led outreach program for high schools in Los Angeles. We developed active learning modules focused on quantitative biology. Here, we describe our outreach effort, key factors that contributed to its success, and the challenges we overcame. We hope that this practical guide may inspire research trainees of all levels to support local schools by participating in science outreach with active learning. We challenge institutions to actively support these efforts.

  PublisherDOI

• A stimulus-contingent positive feedback loop enables IFN-β dose-dependent activation of pro-inflammatory genes

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-08-15

  preprintOpen access1st author

  ABSTRACT Type I interferons (IFN) induce powerful anti-viral and innate immune responses via the transcription factor, IFN-stimulated gene factor (ISGF3). However, in some pathological contexts type I IFNs are responsible for exacerbating inflammation. Here, we show that a high dose of IFN-β also activates an inflammatory gene expression program in contrast to IFN-λ3, a type III IFN, which elicits only the common anti-viral gene program. We show that the inflammatory gene program depends on a second, potentiated phase in ISGF3 activation. Iterating between mathematical modeling and experimental analysis we show that the ISGF3 activation network may engage a positive feedback loop with its subunits IRF9 and STAT2. This network motif mediates stimulus-specific ISGF3 dynamics that are dependent on ligand, dose, and duration of exposure, and when engaged activates the inflammatory gene expression program. Our results reveal a previously underappreciated dynamical control of the JAK-STAT/IRF signaling network that may produce distinct biological responses, and suggest that studies of type I IFN dysregulation, and in turn therapeutic remedies, may focus on feedback regulators within it. HIGHLIGHTS High dose IFN-β activates a pro-inflammatory gene program in epithelial cells. IFN-β, but not IFN-λ3, induces a second, potentiated phase in ISGF3 activity. ISGF3 induces its subunits to form a stimulus-contingent positive feedback loop. The positive feedback motif is required for the pro-inflammatory gene program.

  PublisherOA PDFDOI

• High Dose IFN-β Activates GAF to Enhance Expression of ISGF3 Target Genes in MLE12 Epithelial Cells

  Frontiers in Immunology · 2021 · 6 citations

  • Cell biology
  • Biology
  • Cancer research

  preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states.

  PublisherDOI

• High dose IFN- <i>β</i> activates GAF to enhance expression of ISGF3 target genes in epithelial cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2020-10-28

  preprintOpen access

  Abstract Interferon β (IFN- β ) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN- β activates a second transcription factor, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in respiratory epithelial cells high doses of IFN- β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN- β preferentially activate ISGF3 but not GAF. Surprisingly, in epithelial cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. Our data suggest that GAF enhances ISGF3 target gene expression by co-localizing with ISGF3 at some promoters and facilitating chromosome looping between distal enhancers and other promoters. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states in respiratory epithelial cells. One sentence summary GAF is transcriptionally inactive in epithelial cells but enhances expression of ISGF3 target genes, thus functioning as a dose-sensitive amplifier of the IFN- β response.

  PublisherOA PDFDOI

• Dynamic Model of Protease State and Inhibitor Trafficking to Predict Protease Activity in Breast Cancer Cells

  Cellular and Molecular Bioengineering · 2019-06-19 · 6 citations

  articleOpen access
  PublisherOA PDFDOI

• Pharmacological Protease Inhibitor Preserves Proteolytic Activity In Breast Cancer Cells: Computational Models To Probe Unexpected Cellular Responses

  The FASEB Journal · 2018-04-01

  article

  Cysteine cathepsins are powerful elastases and collagenases, produced by breast cancer cells and tumor associated macrophages, capable of remodeling extracellular matrix and driving tumor growth and metastasis. Cathepsin expression and activity are regulated by endogenous protein inhibitors as well as proteolytic interactive networks that are not completely understood. To date, no cathepsin inhibitors have cleared clinical trials due to side effects including increased stroke risk. Surprisingly, cathepsin inhibitor treatment has been associated with increased cathepsin expression and activity. This unexpected increase in cathepsin activity could be contributing to observed side effects, but mechanisms responsible for this increased activity have not been identified. Furthermore, this increase in activity following inhibitor treatment is not consistent across different members of the cathepsin family. We have previously published that MDA‐MB‐231 breast cancer cells treated with the pharmacological cathepsin inhibitor E64 have increased active cathepsin S and decreased active cathepsin L, despite no change in total detectable cathepsin protein or mRNA. Subsequent experiments have revealed similar responses to E64 in other cancer and macrophage cell lines, suggesting this response to inhibitors is a biological phenomenon, which if elucidated would inform cathepsin inhibitor treatment in cancer. The objective of this work is to use mathematical modeling to test multiple mechanisms capable of explaining cathepsin specific changes in activity following inhibitor treatment. A series of mathematical models were developed in R to test potential hypothesized mechanisms responsible for increased active enzyme following inhibitor treatment. The models consist of series of ordinary differential equations based on principles of generalized mass action, capable of simulating the production, activation, inhibition and degradation of cathepsin L and S in breast cancer cells. This model architecture allows us to investigate different potential regulatory nodes in the cathepsin “life‐cycle”. We have previously published that cathepsins can degrade other cathepsins, a phenomenon we termed cathepsin cannibalism. Our first model tested the hypothesis that E64 was inhibiting cathepsin L, preventing it from degrading active cathepsin S. However, this model was not able to recapitulate the experimental results. We next tested the hypothesis that E64 could be stabilizing cathepsin S, increasing its activity over time. We found that the formation of stable cathepsin S E64 complexes could explain the observed increase in cathepsin S activity, while the loss of cathepsin L activity could be explained by disrupting binding with intracellular substrates or inhibitors. The model also predicted the intracellular production and degradation of cathepsin L is significantly greater than for cathepsin S. This hypothesis was supported experimentally using the translational inhibitor cycloheximide, which revealed cathepsin L intracellular turnover proceeds significantly more quickly than cathepsin S. Taken together, these results suggest that protease inhibitors can cause both accumulation of active proteases as well as depletion of active proteases, with no appreciable change in total protein. This is important to the design and successful application of future protease inhibitors to prevent off‐target inhibition and clinical trial ending side effects. Support or Funding Information This work was funded by NSF CBET‐0939511. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

  PublisherDOI

• MECHANISMS DURING CATHEPSIN INHIBITION AND THE EFFECTS ON SUBSTRATE DEGRADATION AND BREAST CANCER CELL INVASION

  SMARTech Repository (Georgia Institute of Technology) · 2016-04-12

  dissertation1st authorCorresponding

  Cysteine cathepsin proteases are powerful collagenases and gelatinases that play an important role in matrix remodeling and are upregulated in various diseases including breast cancer. During cancer progression, tumor cells upregulate cysteine cathepsins to assist with the invasion and metastasis of the tumor. This has motivated pharmaceutical companies to develop protease inhibitors, but many have not passed through clinical trials not due to the lack of efficacy, but due to adverse side effects. Currently there is limited research investigating cellular feedback mechanisms caused by cathepsin inhibitors. This highlights a need to understand how cathepsin inhibition affects cathepsin production in breast cancer cells. To accomplish this, we investigated the effects two cathepsin inhibitors, the small molecule E-64 and cystatin C protein, have on the cellular regulation of cathepsins. Interestingly, both E-64 and cystatin C caused an upregulation of the amount of active cathepsin S. This was in contrast to cathepsin L which was either downregulated or unchanged. This was due to differences in cellular localization of cathepsins S and L. Inhibitor-induced co-localization of cathepsin S with gelatin substrate and cystatin C inhibitor occurred in the breast cancer cells. However, cathepsin L was located in the cytoplasm instead of with gelatin or cystatin C. This work demonstrates the need to better understand feedback mechanisms within the cathepsin proteolytic network and the cellular responses due to inhibitors for developing effective therapeutics and dosing strategies targeting cysteine cathepsins for the prevention of cancer invasion and metastasis.

  Publisher

• Differential cathepsin responses to inhibitor-induced feedback: E-64 and cystatin C elevate active cathepsin S and suppress active cathepsin L in breast cancer cells

  The International Journal of Biochemistry & Cell Biology · 2016-09-08 · 29 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

Frequent coauthors

• Manu O. Platt

  The Wallace H. Coulter Department of Biomedical Engineering

  20 shared

• Minh Anh Nguyen

  University of California, Los Angeles

  13 shared

• Kensei Kishimoto

  University of Massachusetts Chan Medical School

  13 shared

• Alexander Hoffmann

  10 shared

• Alma Zuniga Munoz

  University of Southern California

  10 shared

• Raisa Mathenge

  University of California, San Francisco

  10 shared

• Quen J. Cheng

  University of California, Los Angeles

  9 shared

• Stefanie Luecke

  8 shared

Awards & honors

• Kirkus Reviews named Ebony & Ivy one of the best nonfiction…
• won multiple book awards
• Peabody Award (2013)