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Heads of Laboratories

Head shot of Hermann Steller
Hermann Steller, Ph.D.
Strang Professor
Strang Laboratory of Apoptosis and Cancer Biology
Hermann.Steller@rockefeller.edu

Cell death plays an important role in sculpting a developing organism and eliminating unwanted and potentially dangerous cells throughout life. Dr. Steller’s research focuses on how programmed cell death is regulated, and how its dysfunction contributes to disease, including cancer. He also studies the nonlethal use of cell death proteins for cellular remodeling, and the mechanism of protein degradation in development, aging, and disease.

Central to both development and tissue homeostasis, apoptosis is intimately associated with a variety of human diseases including cancer, autoimmunity, AIDS, neurodegenerative disorders, and liver diseases. This makes cell death proteins promising drug targets. Using both Drosophila melanogaster and mice as model organisms, Dr. Steller’s laboratory investigates the molecular mechanisms that govern the decision between cell death and survival.

Apoptosis has been conserved in evolution from worms to insects to humans. Dr. Steller’s lab discovered and characterized a family of proteins that act as integrators of many different signaling pathways to ensure that the death program is activated. Reaper, Hid, and Grim activate apoptosis by binding to and inactivating inhibitor of apoptosis (IAP) proteins, which in turn directly inhibit caspases, the key executioners of apoptosis. A conserved IAP-binding motif originally discovered in these proteins has provided the basis for a novel class of cancer therapeutics currently in clinical trials.

Many organs and tissues can repair wounds and regenerate cells lost upon injury. Dr. Steller discovered that cells undergoing apoptosis in response to stress or injury can stimulate their own replacement by secreting mitogens to induce proliferation of adjacent progenitor cells. These mitogen pathways have been highly conserved in evolution, and similar phenomena have been recently observed in mammals, with profound implications for cancer therapy, stem cell biology, and regenerative medicine.

The cell death machinery can also serve nonlethal functions for cellular remodeling in Drosophila and mammals. Dr. Steller’s work initially revealed the importance of this process for the generation of mature sperm, but subsequently similar mechanisms were shown to operate during development of the nervous system. Dr. Steller defined the role of enzymes that control protein degradation by the apoptosis machinery, and his work has revealed that two major proteolytic systems, caspases and proteasomes, are coordinated to achieve “controlled demolition” of unwanted cellular structures. These findings are relevant for human diseases, including muscle-wasting diseases, neuronal degeneration, and cancer.

More recently, work in Dr. Steller’s lab has focused on the mechanisms by which cells degrade unwanted and toxic proteins. The long-term health of cells critically relies on selective protein degradation since damaged or aggregated proteins cause proteotoxic stress that can impair cell function and cause cell death. Many neuro-degenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases, ALS, and retinitis pigmentosa, are caused by the accumulation of protein aggregates. Dr. Steller’s laboratory discovered a mechanism that enables cells to boost their proteolytic capacity by stimulating the assembly of proteasomes, the multi-protein protease complex responsible for the regulated degradation of intracellular proteins. Manipulating the activity of this pathway may lead to novel therapeutics for the treatment of age-related neuro-degenerative diseases.


EDUCATION

Diploma in microbiology and molecular genetics, 1981
University of Frankfurt

Ph.D. in molecular biology, 1984
European Molecular Biology Laboratory and University of Heidelberg

POSTDOC

University of California, Berkeley, 1985–1987

POSITIONS

Assistant Professor, 1987–1992
Associate Professor, 1992–1994
Associate Professor with Tenure, 1994–1996
Professor, 1996–2000
Massachusetts Institute of Technology

Professor, 2000–
The Rockefeller University

Assistant Investigator, 1990–1993
Associate Investigator, 1993–1996
Investigator, 1997–
Howard Hughes Medical Institute

AWARDS

Searle Scholar, 1988

Pew Biomedical Scholar, 1989

SELECTED PUBLICATIONS

Cho-Park, P.F. and Steller, H. Proteasome regulation by ADP-ribosylation. Cell 153, 614–627 (2013).

Fuchs, Y. et al. Sept4/ARTS regulates stem cell apoptosis and skin regeneration. Science 341, 286–289 (2013).

Perez, A. et al. Apoptotic cells can induce non-autonomous apoptosis through the TNF pathway. Elife 2, e01004 (2013).

Bader, M. et al. A conserved F box regulatory complex controls proteasome activity in Drosophila. Cell 145, 371–382 (2011).

Ryoo, H.D. et al. Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways. Dev. Cell 7, 491–501 (2004).


Dr. Steller is a faculty member in the David Rockefeller Graduate Program and the Tri-Institutional M.D.-Ph.D. Program.