About

David Smith, MD, MAS, is an infectious disease specialist and translational research virologist. His primary research involves understanding how to stop the transmission of HIV and developing cures for HIV, with over 200 scientific publications in these areas. He uses basic science techniques to answer clinically relevant questions in his translational research. Dr. Smith was named HIV Researcher of the Year by the HIV Medical Association in 2010 and became the co-director and principal investigator of the San Diego Center for AIDS Research (CFAR) in 2016. Since the outbreak of SARS-CoV-2 in 2019, he has been actively engaged in the international effort to find safe and effective treatments, serving as the international protocol chair for the ACTIV-2 treatment study, part of the US government’s Operation Warp Speed, aimed at identifying therapies for early COVID-19 cases. He completed his medical training at East Tennessee State University School of Medicine in 1996, followed by internship, residency, and fellowship at UC San Diego, where he joined the faculty in 2003 and was promoted to full professor in 2012. In 2017, he was promoted to Head of the Division of Infectious Diseases and Global Public Health at UC San Diego, and in 2020, he was appointed the Florence Seeley Riford Chair in AIDS Research. His work has earned him numerous awards and honors, including election as a fellow of the American Society of Clinical Investigation, the American College of Physicians, and the Infectious Diseases Society of America.

Research topics

• Biology
• Immunology
• Chemistry
• Computer Science
• Cancer research
• Telecommunications
• Anatomy
• Genetics
• Internal medicine
• Nanotechnology
• Materials science
• Biomedical engineering
• Composite material
• Biophysics
• Cell biology
• Medicine

Selected publications

• Supplementary Figure S2 from An Engineered Tumor-on-a-Chip Device with Breast Cancer–Immune Cell Interactions for Assessing T-cell Recruitment

  2023

  • Computer Science
  • Cancer research
  • Medicine

  <p>Figure S2 shows the characterization of the endothelial layer.</p>

  DOI

• Data from An Engineered Tumor-on-a-Chip Device with Breast Cancer–Immune Cell Interactions for Assessing T-cell Recruitment

  2023

  • Cell biology
  • Cancer research
  • Chemistry

  <div>Abstract<p>Recruitment of immune cells to a tumor is determined by the complex interplay between cellular and noncellular components of the tumor microenvironment. <i>Ex vivo</i> platforms that enable identification of key components that promote immune cell recruitment to the tumor could advance the field significantly. Herein, we describe the development of a perfusable multicellular tumor-on-a-chip platform involving different cell populations. Cancer cells, monocytes, and endothelial cells were spatially confined within a gelatin hydrogel in a controlled manner by using 3D photopatterning. The migration of the encapsulated endothelial cells against a chemokine gradient created an endothelial layer around the constructs. Using this platform, we examined the effect of cancer cell–monocyte interaction on T-cell recruitment, where T cells were dispersed within the perfused media and allowed to infiltrate. The hypoxic environment in the spheroid cultures recruited more T cells compared with dispersed cancer cells. Moreover, the addition of monocytes to the cancer cells improved T-cell recruitment. The differences in T-cell recruitment were associated with differences in chemokine secretion including chemokines influencing the permeability of the endothelial barrier. This proof-of-concept study shows how integration of microfabrication, microfluidics, and 3D cell culture systems could be used for the development of tumor-on-a-chip platforms involving heterotypic cells and their application in studying recruitment of cells by the tumor-associated microenvironment.</p>Significance:<p>This study describes how tumor-on-chip platforms could be designed to create a heterogeneous mix of cells and noncellular components to study the effect of the tumor microenvironment on immune cell recruitment.</p></div>

  DOI

• Deciphering the Mechanics of Cancer Spheroid Growth in 3D Environments through Microfluidics Driven Mechanical Actuation

  Advanced Healthcare Materials · 2022 · 15 citations

  • Materials science
  • Biomedical engineering
  • Nanotechnology

  Uncontrolled growth of tumor cells is a key contributor to cancer-associated mortalities. Tumor growth is a biomechanical process whereby the cancer cells displace the surrounding matrix that provides mechanical resistance to the growing cells. The process of tumor growth and remodeling is regulated by material properties of both the cancer cells and their surrounding matrix, yet the mechanical interdependency between the two entities is not well understood. Herein, this work develops a microfluidic platform that precisely positions tumor spheroids within a hydrogel and mechanically probes the growing spheroids and surrounding matrix simultaneously. By using hydrostatic pressure to deform the spheroid-laden hydrogel along with confocal imaging and finite element (FE) analysis, this work deduces the material properties of the spheroid and the matrix in situ. For spheroids embedded within soft hydrogels, decreases in the Young's modulus of the matrix are detected at discrete locations accompanied by localized tumor growth. Contrastingly, spheroids within stiff hydrogels do not significantly decrease the Young's modulus of the surrounding matrix, despite exhibiting growth. Spheroids in stiff matrices leverage their high bulk modulus to grow and display a uniform volumetric expansion. Collectively, a quantitative platform is established and new insights into tumor growth within a stiff 3D environment are provided.

  DOI

Frequent coauthors

• Shyni Varghese

  Duke University

  34 shared

• Aereas Aung

  University of Toronto

  31 shared

• Jomkuan Theprungsirikul

  Duke University

  30 shared

• Vardhman Kumar

  Duke University

  26 shared

• Han Liang Lim

  5 shared

• Sukriti Dewan

  Loyola University Chicago

  4 shared

• Andrew D. McCulloch

  University of California, San Diego

  4 shared

• Ivneet Singh Bhullar

  La Jolla Bioengineering Institute

  4 shared

Education

• M.A.S, Clinical Research, Medicine

  University of California San Diego

  2005

• M.D.

  East Tennessee State University James H Quillen College of Medicine

  1996

• B.S., Biology

  University of Tennessee at Chattanooga

  1992

Awards & honors

• HIV Researcher of the Year by the HIV Medical Association (2…
• Avant Garde Award for HIV (2012)
• Fellow American College of Physicians (2014)
• Fellow Infectious Disease Society of America (2015)
• Fellow American Society of Clinical Investigation (2014)

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