Senior Director, Pathology
"Harnessing scientific inquiry for the development of new drugs is an exciting and important endeavor and is made especially satisfying by the scientifically rigorous environment at Genentech."
years at Genentech
awards & honors
I joined Genentech in 2008 as Senior Director of Pathology, after having spent more than 18 years as an HHMI Investigator at the University of Michigan and then 3 years as Chair of Pathology at Case Western Reserve University School of Medicine. The role of Senior Director of Pathology in Research at Genentech offered attractive opportunities to do research in an outstanding, disease-focused scientific environment, while also helping to lead the scientific and research support activities of the Pathology department. These latter efforts help Genentech continue to make a major positive difference to the health and well being of a large number of patients afflicted with cancer, autoimmune syndromes, neurodegenerative diseases and other illnesses for which therapies are unsatisfactory or nonexistent.
An exceptional team of pathologists, laboratory managers, scientific associates and administrative staff in the department collaborate with me in these efforts. Additional outstanding pathologists, scientists, and managers continue to be recruited to assist us in ensuring that the department performs at the highest level. Our task is made more straightforward by the environment at Genentech, which is characterized by exceptionally bright, motivated and collaborative colleagues at every level, spectacular facilities, and workplace philosophies that are conducive to the highest levels of achievement.
The opportunity to mentor postdoctoral fellows at Genentech has been a stimulating and gratifying experience for me. This derives in part from the freedom afforded by the program to pursue research directions that are deemed to be important and interesting, even if these have no immediate therapeutic relevance. The special mentoring experience also derives from extraordinary breadth and quality of the core laboratories at Genentech, and the spectacular intellectual environment. Together, these circumstances provide an unparalleled opportunity for postdoctoral fellows, and their mentors, to engage in biomedical discovery of the highest caliber.
Therapeutic antibodies reveal Notch control of transdifferentiation in the adult lung.
Nature, 2015, ISSN: 0028-0836
Lafkas D, Shelton A, Chiu C, de Leon Boenig G, Chen Y, Stawicki SS, Siltanen C, Reichelt M, Zhou M, Wu X, Eastham-Anderson J, Moore H, Roose-Girma M, Chinn Y, Hang JQ, Warming S, Egen J, Lee WP, Austin C, Wu Y, Payandeh J, Lowe JB, Siebel CW.
One major focus of our laboratory research is to better understand post-transcriptional control of expression and function of members of the Notch family of trans-membrane signaling receptors. These efforts include developing a better understanding of the post-translational glycan modifications on Notch family members, and on their ligands. This work includes studies designed to understand the nature of such modifications, including novel ones, and how these are elaborated and controlled. We ultimately seek to better understand how such modifications control Notch-dependent signal transduction, and how such modifications modulate the biology of the cells that express them, including especially cells within the hematopoietic lineages. We also seek to understand post-transcriptional control of the expression of Notch family members in the hematopoietic system. Efforts are underway to identify molecules and mechanisms responsible for such control, and to develop an understanding of the relevance of such regulation to function in the immune system.
A second major focus of our research centers on understanding how specific glycan structures on immunoglobulins modulate their interaction with NK cells, and how such modulation in turn controls the ability of NK cells to engage in antibody-dependent cytotoxicity towards tumor cell targets. These studies derive from pre-clinical research, and clinical trial observations. We seek to understand the molecules and mechanisms that are relevant to the specific cellular interactions that are characteristic of the glycoengineered antibodies.
Training the next generation of biomedical investigators in glycosciencesClinical Investigation, 2016, View on PubMed
Implications of understanding the signaling, cellular, and cytotoxic mechanisms afforded by afucosylated antibodiesOncoImmunology, 2015, ISSN: 2162-402X View on PubMed
Notch Receptor-Ligand Engagement Maintains Hematopoietic Stem Cell Quiescence and Niche RetentionStem cells (Dayton, Ohio), 2015, ISSN: 1066-5099 View on PubMed
Multiplexed ion beam imaging of human breast tumorsNature Medicine, 2014, ISSN: 1078-8956 View on PubMed
Introduction for the Special Issue on Glycosylation and ImmunitySeminars in Immunopathology, 2012, ISSN: 1863-2297 View on PubMed
Protein O-fucosyltransferase 1 (Pofut1) regulates lymphoid and myeloid homeostasis through modulation of Notch receptor ligand interactions.BLOOD, 2011, V117, N21, MAY 26, pp 5652-5662. ISSN: 0006-4971. View on PubMed
O-Fucose Modulates Notch-Controlled Blood Lineage Commitment.American Journal of Pathology, 2010, ISSN: 0002-9440 View on PubMed
Secretory Cell Hyperplasia and Defects in Notch Activity in a Mouse Model of Leukocyte Adhesion Deficiency Type IIGastroenterology, 2009, ISSN: 0016-5085 View on PubMed
Fucosyltransferase IV and VII-directed selectin ligand function determines long-term survival in experimental tuberculosis.Immunobiology, 2009, ISSN: 0171-2985
- Washington University School of Medicine, Post-doctoral Fellowships – 1984
- Washington University School of Medicine, Laboratory Medicine, Resident – 1983
- University of Utah College of Medicine, M.D. – 1980
- University of Wyoming, Mathematics, B.A. – 1976
Awards & Honors
- Henry Willson Payne Professorship at Case Western Reserve University School of Medicine – 2005
- Elected Fellow, American Association for the Advancement of Science – 2002
- Elected Member, American Association of Physicians – 1999
- American Society of Clinical Pathologists Philip Levine Outstanding Research Award – 1997
- Warner Lambert/Parke Davis Professorship in Medicine at the University of Michigan School of Medicin – 1994
- Elected Member, American Society for Clinical Investigation – 1994
- Howard and Martha Holley Symposium Research Prize in Rheumatology, American College of Rheumatology – 1993
- Warner-Lambert/Parke-Davis Award in Experimental Pathology – 1992
- American Cancer Society Postdoctoral Fellow – 1983
- Phi Beta Kappa, University of Wyoming – 1975