CRISPR-Cas engineering to unravel cellular signaling in cancer progression and therapy

The Fellmann Lab focuses on unraveling organizational principles of cellular signaling networks in cancer progression and therapy. Fellmann’s work has centered on better understanding RNA-guided immune systems, including RNAi and CRISPR-Cas machinery, and leveraging them to dissect cancer, with a particular focus on RAS-mutant tumors and glioblastoma. His lab studies the mechanistic interplay between CRISPR‐Cas enzymes and mammalian DNA repair pathways to pioneer innovative approaches for genome manipulation and precision medicine. Fellmann and his team apply these methods to study the plasticity of cellular signaling networks and their rewiring in cancers, with the ultimate goal of translating insights into clinically actionable strategies to treat patients.

Disease Areas

Cancer
Brain Cancer, Glioblastoma
Cell Signaling Disorders
Neuroscience

Areas of Expertise

CRISPR and Genome Editing
Cancer Biology
Glioblastoma
Functional Genomics
Synthetic Biology
RNA Interference
Working in the Fellmann lab

Lab Focus

Unravel organizational principles of cellular communication and its rewiring during brain cancer progression and therapy
Understand the interplay between CRISPR-Cas enzymes and mammalian DNA repair pathways
Pioneer innovative CRISPR-Cas approaches for genome manipulation and precision medicine

Research Impact

Glioblastoma (GBM) is the most common and lethal primary brain cancer in adults. Despite multimodal treatment regimens including surgical resection, radiotherapy and chemotherapy, GBM remains one of the most challenging cancers to treat, and the median survival of GBM patients is 12-15 months. GBMs are highly diffuse and exhibit extensive intratumoral heterogeneity, with subpopulations of cells displaying distinct mutations, copy number aberrations, gene expression patterns, and epigenetic states. This confounds diagnostic efforts and presents an opportunity for the cancer to evade therapy. Hence, there is an urgent need to establish innovative treatment strategies that can target and efficiently eliminate GBM cells in vivo irrespective of their mutational and epigenetic profile.

Fellmann and his team focus on understanding principles of cellular communication and its rewiring in brain cancer by pioneering synthetic biology tools and applying them to cell culture and in vivo models for the development of innovative, clinically actionable glioblastoma therapies. Specifically, CRISPR-Cas9 enzymes are RNA-guided DNA endonucleases enabling programmable introduction of DNA double-strand breaks at target loci throughout the genome. Their discovery and establishment as tools for genome editing and manipulation has revolutionized biomedicine. Yet, the translation of CRISPR-Cas technologies to clinical applications still faces a number of hurdles, including the possibility of off-target effects and the difficulty of in vivo delivery. Through their efforts to optimize the safety and flexibility of these methods, Fellmann and his team help unravel the complexities of cellular signaling and transform CRISPR-Cas from a tool for discovery to a therapeutic modality that can be deployed for precision medicine.

 

Professional Titles

Research Investigator, Gladstone Institutes

Assistant Adjunct Professor, Department of Cellular and Molecular Pharmacology, School of Medicine, UC San Francisco

Bio

Christof Fellmann holds an undergraduate degree (Vordiplom – BSc equivalent) from the University of Basel, Switzerland, an Engineering Degree in Biotechnology (Dipl. Ing. Biotech. – MSc equivalent) from the Ecole Supérieure de Biotechnologie, Strasbourg, France, and a PhD in Molecular Life Sciences from Cold Spring Harbor Laboratory, USA / University of Zurich, Switzerland.

Fellmann did his PhD work under the guidance of Dr. Scott Lowe at Cold Spring Harbor Laboratory, working on cancer modeling and large-scale screening. Developing high-throughput methods, he investigated mechanistic requirements of microRNA biogenesis (Fellmann et al., Mol Cell, 2011) and leveraged this insight to develop state-of-the-art RNAi tools (Fellmann et al., Cell Rep, 2013; Pelossof et al., and Fellmann, Nat Biotechnol, 2017). In turn, they used these tools to uncover signaling networks in RAS-mutant cancer (Yuan*, Fellmann*, Lee* et al., Cancer Discov, 2014), among others.

After establishing his own company building genetically engineered mouse models, Fellmann trained as postdoctoral fellow with Jennifer Doudna at UC Berkeley, focusing on regulation of CRISPR-Cas enzymes, including circular permutation of Cas9 for precise fusion proteins and protease-activated ProCas9s for tissue-specific genome editing (Oakes*, Fellmann* et al., Cell, 2019). Concurrently, he deployed advanced CRISPR methods to discover synthetic lethal therapeutic dependencies in TERT-promoter mutant glioblastoma (Amen*, Fellmann* et al., PNAS).

How Did You Get Your Start in Science?

“Curiosity to explore the unknown.”

Christof Fellmann, PhD

Honors and Awards

2021 R35 Maximizing Investigators’ Research Award (MIRA) for ESI. NIH, National Institute of General Medical Sciences (NIGMS).

2021 UCSF Brain Tumor SPORE Developmental Research Program (DRP) award. NIH, National Cancer Institute (NCI).

2021 The Ivy Seminar Series, Ivy Brain Tumor Center at the Barrow Neurological Institute. Invited seminar

2021 Society for Neuro-Oncology (SNO) Annual Meeting, Boston, MA. Oral presentation

2020 Gladstone Science Talks seminar. Gladstone Institutes, San Francisco, CA.

2019 UCSF Brain Tumor SPORE Career Enhancement Program (CEP) award, NIH, National Cancer Institute (NCI).

2019 8th Annual Congress on Cancer Metastasis, San Francisco, USA, Invited talk

2019 Microbiology Society Annual Conference 2019, Belfast, UK, Prize medal lecture

2018 Cancer Research: A Joint Celebration Meeting, Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, Brazil, Keynote address

2017 American College of Rheumatology, Association of Rheumatology Health Professionals (ACR/ARHP), Annual Meeting, San Diego, USA, State-of-the-Art lecture

2017 Swiss Academy of Pharmaceutical Sciences, 10th Swiss Pharma Science Day, Bern, Switzerland, Plenary lecture

2017 Workshop on Pancreatic Cancer, Cold Spring Harbor Laboratory, Cold Spring Harbor, USA, Selected participant

2017 International Society for Heart and Lung Transplantation, 37th Annual Meeting and Scientific Sessions, San Diego, USA, Invited talk

2017 American Association for Cancer Research (AACR), Annual Meeting 2017, Washington, DC, USA, Invited speaker, educational session

2017 24th International Molecular Med Tri-Conference, San Francisco, USA, Invited talk

2016 Pathway to Independence Award (K99/R00), NIH, National Institute of General Medical Sciences (NIGMS)

2016 American Transplant Congress, Annual Meeting 2016, Boston, USA, State-of-the-Art address

2015 Discovery On Target, New Frontiers in Gene Editing, Boston, USA, Invited talk

2015 11th KOGO Winter Symposium, Korea Genome Organization, Hongcheon, Korea, Invited talk

2014 Small Business Innovation Research (SBIR) grant. National Institutes of Health (NIH).

2014 Translational Cancer Research for Basic Scientists workshop, AACR, Dana-Farber Cancer Institute/Harvard Cancer Center, Boston, USA, Selected participant

2014 RNA Silencing, Keystone Symposia, Seattle, USA,Invited talk

2013 8th Microsymposium on Small RNAs, IMBA, Vienna, Austria, Invited talk

2011 Elected Member of the Science Program for Excellence in Science, American Association for the Advancement of Science (AAAS)

2011 BioVision.Nxt fellow, BioVision, 7th World Life Sciences Forum, Lyon, France

2008 Novartis European Biotechnology Leadership Camp, Basel, Switzerland, Selected participant

2005 Chairman of the French Charter of the Young European Biotech Network (YEBN)

Publications

More Publications

Contact

Christof Fellmann
Email
415.734.2541


Lab Members