About

Alexander C Huang, MD, is an Assistant Professor of Medicine in the Department of Medicine at the Perelman School of Medicine at the University of Pennsylvania. His professional focus includes hematology-oncology, with a particular emphasis on cancer immunotherapy and immune responses. Dr. Huang is involved in research that explores the mechanisms of immune responses in cancer treatment, including the effects of combination therapies such as anti-PD-1 and anti-CTLA-4, and the immune microenvironment in melanoma. His work contributes to understanding how immune responses can be optimized for better therapeutic outcomes, and he has authored multiple publications in this field. Dr. Huang is affiliated with graduate groups in Cell and Molecular Biology and Immunology, and he is actively engaged in advancing cancer immunology research.

Research topics

• Medicine
• Immunology
• Biology
• Internal medicine
• Computer Science
• Cancer research
• Genetics
• Pathology
• Evolutionary biology
• Microbiology
• Oncology
• Cell biology
• Virology
• Computational biology

Selected publications

• Signaling Through FcγRIIA and the C5a-C5aR Pathway Mediate Platelet Hyperactivation in COVID-19

  Frontiers in Immunology · 2022 · 54 citations

  • Medicine
  • Immunology
  • Internal medicine

  platelet activation. Mechanistically, blocking the signaling of the FcγRIIa-Syk and C5a-C5aR pathways on platelets, using antibody-mediated neutralization, IgG depletion or the Syk inhibitor fostamatinib, reversed this hyperactivity driven by COVID-19 plasma and prevented platelet aggregation in endothelial microfluidic chamber conditions. These data identified these potentially actionable pathways as central for platelet activation and/or vascular complications and clinical outcomes in COVID-19 patients. In conclusion, we reveal a key role of platelet-mediated immunothrombosis in COVID-19 and identify distinct, clinically relevant, targetable signaling pathways that mediate this effect.

  PublisherOA PDFDOI

• CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer

  Nature Medicine · 2021 · 512 citations

  Senior authorCorresponding
  • Medicine
  • Immunology
  • Internal medicine
  DOI

• Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms

  Immunity · 2020 · 1028 citations

  • Biology
  • Genetics
  • Evolutionary biology
  DOI

• Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications

  Science · 2020 · 1652 citations

  • Computer Science
  • Virology
  • Biology

  Immune profiling of COVID-19 patients Coronavirus disease 2019 (COVID-19) has affected millions of people globally, yet how the human immune system responds to and influences COVID-19 severity remains unclear. Mathew et al. present a comprehensive atlas of immune modulation associated with COVID-19. They performed high-dimensional flow cytometry of hospitalized COVID-19 patients and found three prominent and distinct immunotypes that are related to disease severity and clinical parameters. Arunachalam et al. report a systems biology approach to assess the immune system of COVID-19 patients with mild-to-severe disease. These studies provide a compendium of immune cell information and roadmaps for potential therapeutic interventions. Science , this issue p. eabc8511 , p. 1210

  DOI

• Association of Antibiotic Exposure With Survival and Toxicity in Patients With Melanoma Receiving Immunotherapy

  JNCI Journal of the National Cancer Institute · 2020 · 135 citations

  • Medicine
  • Oncology
  • Internal medicine

  BACKGROUND: Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival. METHODS: Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was prespecified. The primary outcome was overall survival (OS), and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous steroids. All statistical tests were two-sided. RESULTS: There were 568 patients in our database of which 114 received antibiotics prior to ICI. Of the patients, 35.9% had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] = 1.81, 95% confidence interval [CI] = 1.27 to 2.57; P <.001). The same effect was observed among antibiotic-exposed patients with stage III disease (HR = 2.78, 95% CI = 1.31 to 5.87; P =.007). When limited to only patients who received adjuvant ICI (n = 89), antibiotic-exposed patients also had statistically significantly worse OS (HR = 4.84, 95% CI = 1.09 to 21.50; P =.04). The antibiotic group had a greater incidence of colitis (HR = 2.14, 95% CI = 1.02 to 4.52; P =.046). CONCLUSION: Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.

  DOI

Recent grants

• Role of tumor burden in limiting durable reinvigoration by PD-1 blockade

  NIH · $1.0M · 2019–2024

Frequent coauthors

• E. John Wherry

  University of Pennsylvania

  275 shared

• Josephine R. Giles

  University of Pennsylvania

  116 shared

• Lynn M. Schuchter

  University of Pennsylvania

  107 shared

• Tara C. Mitchell

  102 shared

• Sasikanth Manne

  University of Pennsylvania

  101 shared

• Ravi K. Amaravadi

  101 shared

• Divij Mathew

  University of Pennsylvania

  88 shared

• Xiaowei Xu

  The Wistar Institute

  74 shared

Labs

• Alexander C Huang LaboratoryPI

Education

• B.S., Science, Biomedical Engineering

  Johns Hopkins University

  2005

• M.D.

  Mount Sinai School of Medicine

  2010

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