Stefan Grotegut's Research Focus
Dr. Grotegut is group leader and senior scientist at Sanford Burnham Prebys Medical Discovery Institute, where he oversees assay development efforts for implementing large (<710,000 compounds) high-throughput screens. Resources for these efforts include state of the art ultra-High Throughput Drug Screening and lead discovery capabilities.
Dr. Grotegut’s overall goal is to identify new targets for the development of small molecule therapeutics and guide his team through the process of generating new assays, executing primary screening, as well as hit follow-up, hit-to-lead, and lead optimization studies, and mode of action analysis. Dr. Grotegut’s project portfolio of highly interactive research programs include investigators from the institute and partners from pharmaceutical industry.
Since joining the Prebys Center in 2011, Dr. Grotegut has successfully developed and managed more than 20 screening campaigns generating over 10 million screening data points in 6 disease areas. Dr. Grotegut works closely with other teams at the Prebys Center to support the full pre-clinical drug discovery pipeline enabling the overall mission of the Institute to translate basic research to new products.
Stefan Grotegut's Bio
Dr. Grotegut has many years of drug discovery and assay development experience within the Prebys Center. He is critically involved in a multitude of projects with both academic and pharmaceutical industry partners. He leads projects from the planning phase through execution and analysis stage, and ensures high quality data generation and reporting. This includes biochemical, biophysical, cell-based and phenotypical screens. Dr. Grotegut has an extensive background in tumor biology, and for more than 12 years has investigated the onset and progression of various tumors.
Directly prior to joining the Prebys Center in 2011, he was a Postdoc in the laboratories of Dr. Charles Spruck at the Sidney Kimmel Cancer Center and at SBP. During his postdoc, he investigated in detail the role of SCF-E3 ligases in the ubiquitin-proteasome pathway and its implication in tumor onset and progression. This was important groundwork for identifying and further investigating key E3 ligases and determining their substrates.
Dr. Grotegut received his Ph.D. from the Department of Biomedicine at the University of Basel in Switzerland. In the group of Dr. Gerhard Cristofori, he unraveled a key signaling mechanism by which malignant tumors overcome cell-cell adhesion and to invade surrounding tissue by a process referred to as epithelial-mesenchymal-transition (EMT). During his Master’s thesis in the Human and Environmental Toxicology group at the University of Konstanz, Germany, Dr. Grotegut investigated the toxicity of mycotoxins on human kidney cells and established a model how certain kidney nephropathies, including kidney cancer, can arise.
- Master thesis (2000-2001) identified a possible mechanism of kidney fibrosis and cancer upon mycotoxin exposure. Results were presented at the annual Society of Toxicology (SOT) meeting in San Francisco, CA.
- Discovered how Hepatocyte Growth Factor (HGF) via the MAPK/ERK pathway upregulates the master regulator and transcription factor SNAIL and thereby initiates the multi-stage process of epithelial-mesenchymal transition (EMT), which leads to the conversion of epithelial, differentiated cells to mesenchymal, migratory and invasive cells and thus allows cancer cells to seed and grow metastases in distant organs. In addition, it we demonstrated how HGF signaling contributes to drug resistance and causes cancer cells to evade therapeutic intervention.
- Received Postdoctoral Fellowship Award by the Swiss National Science Foundation (SNF): “F-box Proteins in Cell Cycle Control and Tumorigenesis” (2007 – 2008)
- Received Postdoctoral Fellowship Award by the California Breast Cancer Research Program (CBCRP): “Global Analysis of Protein Ubiquitination in Breast Cancer” (2008 – 2011)
- Co-developed a human proto-array on genome-wide basis to identify a ubiquitination signature of cancer cells undergoing metastasis. With the use of an isogenic mouse model of tumor metastasis a ubiquitination signature was determined for each stage of metastasis and laid the groundwork for identifying new targets and biomarkers of malignant tumors.
- Leads multiple drug discovery projects with both academic and pharmaceutical industry partners from target identification, strategy planning, resourcing, assay development, high-throughput and high-content screening, hit confirmation, hit-to-lead, structure–activity relationship assays, and mode-of-action analysis.
Honors & Awards
- The Fishman Fund Award and Founder’s Price (2010)
- Best Presentation Award, SBMRI Signal Transduction Program (2010)
- AACR Scholar-In-Training Award by Susan G. Komen for the Cure (2009)
- AACR Scholar-In-Training Award by Aflac, Inc. (2009)
- Postdoctoral Fellowship Award by the California Breast Cancer Research Program (CBCRP): “Global Analysis of Protein Ubiquitination in Breast Cancer” (2008 – 2011)
- Postdoctoral Fellowship Award by the Swiss National Science Foundation (SNF): “F-box Proteins in Cell Cycle Control and Tumorigenesis” (2007 – 2008)
- 21st Schweisguth Prize of the International Society of Pediatric Oncology (2006)
- Travel Award of the Signal Transduction Society (2002)
Grotegut S, von Schweinitz D, Christofori G, Lehembre F
EMBO J 2006 Aug 9 ;25(15):3534-45
Hepatocyte growth factor protects hepatoblastoma cells from chemotherapy-induced apoptosis by AKT activation.
Grotegut S, Kappler R, Tarimoradi S, Lehembre F, Christofori G, Von Schweinitz D
Int J Oncol 2010 May ;36(5):1261-7
Endothelin receptor type B counteracts tenascin-C-induced endothelin receptor type A-dependent focal adhesion and actin stress fiber disorganization.
Lange K, Kammerer M, Hegi ME, Grotegut S, Dittmann A, Huang W, Fluri E, Yip GW, Götte M, Ruiz C, Orend G
Cancer Res 2007 Jul 1 ;67(13):6163-73
SBI-0640756 Attenuates the Growth of Clinically Unresponsive Melanomas by Disrupting the eIF4F Translation Initiation Complex.
Feng Y, Pinkerton AB, Hulea L, Zhang T, Davies MA, Grotegut S, Cheli Y, Yin H, Lau E, Kim H, De SK, Barile E, Pellecchia M, Bosenberg M, Li JL, James B, Hassig CA, Brown KM, Topisirovic I, Ronai ZA
Cancer Res 2015 Dec 15 ;75(24):5211-8
Robichaud N, del Rincon SV, Huor B, Alain T, Petruccelli LA, Hearnden J, Goncalves C, Grotegut S, Spruck CH, Furic L, Larsson O, Muller WJ, Miller WH, Sonenberg N
Oncogene 2015 Apr 16 ;34(16):2032-42
Tautz L, Critton DA, Grotegut S
Methods Mol Biol 2013 ;1053:179-221