Daniel Simmons, M.D., Distinguished Scholar Lecture Idiopathic Pulmonary Fibrosis: A Disease in Search of a Cause

Daniel Simmons, M.D., Distinguished Scholar Lecture

March 23, 2023 5:30-7pm

Idiopathic Pulmonary Fibrosis: A Disease in Search of a Cause

by Dr. Tushar Desai

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Biography:

I am a practicing pulmonary physician committed to basic and translational research in lung biology. My initial studies during fellowship investigated the role of retinoic acid signaling in regulating lung bud morphogenesis in the embryonic foregut. Since then, I have focused on integrating genetics, single-cell analysis, ex vivo assays, and advanced multiplex tissue staining techniques to achieve fundamental insights into lung developmental, stem cell, and cancer biology. These efforts have had a major impact on the lung field. I molecularly characterized a bipotent embryonic lung progenitor that directly gives rise to alveolar epithelial type I (AT1) and AT2 cells, then used single-cell RNA-sequencing to generate a molecular atlas of differentiation. I co-developed a novel technique for massively expanding primary human AT2 cells in 3D culture under chemically defined conditions without feeder cells, a first of its kind assay which enables dissecting molecular regualation of the AT2 cell phenotype. I identified an AT2 stem cell that is a cell of origin of lung adenocarcinoma, showed that Wnt is a key regulator of AT2 cell stemness, and identified distinct paracrine and autocrine stem cell signaling niches in aging and injury, respectively. This niche visualization was enabled by a novel multiplex in situ hybridization technology (PLISH) I co-invented for single-cell RNA expression profiling in intact human tissue. We have gone on to generate a 2.0 technology involving tissue embedding in a hydrogel (TEC, Tether Embed Clear) that facilitates 3D, multimodal (protein and nucleic acids), and multiplex staining at single-cell resolution. TEC staining provides spatial information essential for mapping active signaling centers in health and disease and can be used to localize the cell classes identified by tissue dissociative scRNA-seq directly in intact tissue. Currently, my lab focuses on understanding the role of alveolar stem cells in repairing acute lung injury, and how they participate in the pathogenesis of fatal diseases like lung adenocarcinoma and pulmonary fibrosis. I also have a long-term collaboration with Dr. Jayakar Nayak and several other investigators involving CRISPR gene correction of CFTR in upper airway basal stem cells collected from patients with cystic fibrosis. We are working in an animal model to develop this as an autologous stem cell therapy for cystic fibrosis sinus disease.

A major part of my effort is devoted to teaching and mentoring medical and graduate students as well as medical residents and fellows training in clinical medicine. I provide annual lectures to stem cell graduate students on endoderm development and clinical application of stem cell therapies, to pulmonary fellows on sarcoidosis and lung developmental anomalies, and to medical students on airflow obstruction. I also serve as a discussion leader for medical student journal clubs in Molecular Foundations of Medicine and Applied Biochemistry. I expend considerable energy ensuring that my lab environment is accepting, inclusive, and supportive for trainees to be able to excel in conducting ethically sound, responsible research at the highest possible standard. I am committed to actively fostering diversity within my lab and the overall Stem Cell Institute, for which I serve as Director of Graduate Studies. I meet with each lab member one-on-one at least once every two weeks, and have formal lab group meetings and journal clubs where we interact together.

Education: 

Amherst College, Amherst, MA B.A.; Psychology

Tufts University School of Medicine, Boston, MA M.D.

Tufts University School of Medicine, Boston, MA M.P.H.

University of Michigan Hospitals, Ann Arbor, MI Residency;  Internal Medicine

Boston Medical Center, Boston, MA Fellowship; Pulmonary & Critical Care Medicine

Stanford University School of Medicine, Stanford, CA Postdoctoral; Lung development

Positions and Scientific Appointments

Professor of Medicine, Department of Internal Medicine, Division of Pulmonary & Critical Care

Medicine, Stanford University School of Medicine, Stanford, CA

Member, Lung Injury, Repair and Regeneration (LIRR) Study Section, NIH/NHLBI

Director, Graduate Studies, Institute for Stem Cell Biology and Regenerative Medicine,

Stanford University School of Medicine

Robert A. and Gertrude T. Hudson Endowed Professor

Member, Stanford PSTP admissions committee

Co-Director of Admissions, Stem Cell Biology and Regenerative Medicine PhD program

Director, Translational Lung Biology, Department of Internal Medicine, Stanford University

School of Medicine, Stanford, CA

Research Advisor, 15th Annual Respiratory Disease Young Investigators’ Forum

Member, Scientific Advisory Board, UK Regenerative Medicine Platform Engineered Cell

Environment Hub

Associate Professor of Medicine, Department of Internal Medicine, Division of Pulmonary &

Critical Care Medicine, Stanford University School of Medicine, Stanford, CA

Woods Family Faculty Scholar in Pediatric Translational Medicine, Maternal & Child Health

Research Institute, Stanford University School of Medicine

Member, Scientific Advisory Committee, American Thoracic Society