Daryl Klein, MD, PhD
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Research Summary
Dr. Klein is an M.D./Ph.D. trained scientist whose research addresses fundamental problems in cancer signal transduction. His research to date has centered on mechanistic aspects of signaling by receptor tyrosine kinases and other receptors, providing lessons that are central in the quest for new therapeutic opportunities. His work also extends to cytokine and immune cell receptors, where the next generation of targeting signaling therapeutics will surely emerge.
Specialized keywords: receptor signaling; functional selectivity; modulation
Extensive Research Description
Dr. Klein is a trained physician-scientist committed to studying the molecular mechanisms of cancer, and ways to control pathways that lead to metastases. Both personally and as a medical professional, he has witnessed the devastation that cancer causes and its toll on families. This drives him everyday to find new and different ways to approach treatment strategies. Over the past two decades, Dr. Klein's basic science research has spanned multiple aspects of information transfer across biological membranes. Perception of environmental information across this barrier is essential for proper development and health - allowing each cell to know its "time" and "place" in a tissue. This circuitry can go awry in cancer, usurping the typical development logic-gates for adventitious growth. Dr. Klein's independent research focus is to decipher the underlying logic of signal integration across membranes to better understand how disease states take advantage of these signaling "codes." These codes are written in the three dimensional structures, kinetics and regulation of receptor activation. Ultimately, with physical and mathematical models of this signaling logic, Dr. Klein hopes to design synthetic circuitry to override the disease program, driving cells away from metastatic potential and enhancing the body's own targeted immune response. His goal is to bring together ideas from disparate fields including signaling, virology, biophysics, and high throughput screening - to realize the potential of "tuning" receptor activity to control metastatic disease.
Coauthors
Research Interests
Medical Oncology; Pharmacology
Selected Publications
- Discovery of the First Pathogenic Human EPO Mutation Provides Mechanistic Insight into Cytokine SignalingKim A, Ulirsch J, Wilmes S, Unal E, Moraga I, Karakukcu M, Yuan D, Kazerounian S, Gupta N, Gabriel S, Lander E, Patiroglu T, Ozcan A, Ozdemir M, Garcia C, Piehler J, Gazda H, Klein D, Sankaran V. Discovery of the First Pathogenic Human EPO Mutation Provides Mechanistic Insight into Cytokine Signaling Blood 2016, 128: 331-331. DOI: 10.1182/blood.v128.22.331.331.
- Structural basis for EGFR ligand sequestration by ArgosKlein D, Stayrook S, Shi F, Narayan K, Lemmon M. Structural basis for EGFR ligand sequestration by Argos The FASEB Journal 2009, 23: 883.7-883.7. DOI: 10.1096/fasebj.23.1_supplement.883.7.
- ErbB2/HER2/Neu resembles an autoinhibited invertebrate EGF receptorAlvarado D, Klein D, Lemmon M. ErbB2/HER2/Neu resembles an autoinhibited invertebrate EGF receptor The FASEB Journal 2009, 23: 884.3-884.3. DOI: 10.1096/fasebj.23.1_supplement.884.3.
- High-Affinity Binding of a FYVE Domain to Phosphatidylinositol 3-Phosphate Requires Intact Phospholipid but Not FYVE Domain Oligomerization †Sankaran V, Klein D, Sachdeva M, Lemmon M. High-Affinity Binding of a FYVE Domain to Phosphatidylinositol 3-Phosphate Requires Intact Phospholipid but Not FYVE Domain Oligomerization † Biochemistry 2001, 40: 8581-8587. PMID: 11456498, DOI: 10.1021/bi010425d.
- Specificity and Promiscuity in Phosphoinositide Binding by Pleckstrin Homology Domains*Kavran J, Klein D, Lee A, Falasca M, Isakoff S, Skolnik E, Lemmon M. Specificity and Promiscuity in Phosphoinositide Binding by Pleckstrin Homology Domains* Journal Of Biological Chemistry 1998, 273: 30497-30508. PMID: 9804818, DOI: 10.1074/jbc.273.46.30497.
- The Pleckstrin Homology Domains of Dynamin Isoforms Require Oligomerization for High Affinity Phosphoinositide Binding*Klein D, Lee A, Frank D, Marks M, Lemmon M. The Pleckstrin Homology Domains of Dynamin Isoforms Require Oligomerization for High Affinity Phosphoinositide Binding* Journal Of Biological Chemistry 1998, 273: 27725-27733. PMID: 9765310, DOI: 10.1074/jbc.273.42.27725.