Dr. Daniel Schramek

PhD
Senior Investigator

Lunenfeld-Tanenbaum Research Institute
Deputy Director, Discovery Research, Sinai Health

Our lab is dedicated to revolutionizing cancer treatment through functional genomics, aiming for personalized and highly specific therapies. We focus on identifying novel treatments for the most aggressive cancers by systematically uncovering genotype-specific vulnerabilities – the unique weaknesses of cancer cells based on their genetic makeup.

A cornerstone of our research is the development and application of cutting-edge direct in vivo gene-editing tools. This innovative approach allows us to seamlessly integrate complex human cancer genomics data with sophisticated mouse modeling. By doing so, we can functionally assess the roles of hundreds of putative cancer genes, evaluating their capacity to drive tumor formation (tumorigenesis) and spread (metastasis) directly within a living organism. This approach takes into account the critical interactions between cancer cells and their environment that cannot be replicated in a laboratory dish.

This powerful combination of high-throughput screening, advanced gene-editing technology and relevant in vivo models enables us to rapidly pinpoint critical cancer drivers and dependencies. Ultimately, our goal is to translate these fundamental discoveries into new therapeutic strategies, paving the way for more effective and tailored treatments for patients battling devastating malignancies. We believe this direct functional assessment in a physiological context is key to accelerating the discovery of impactful cancer therapies.

Telephone
Contact

Phone: 416-586-8262

Email: [email protected]

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Location

Room 1084, 600 University Avenue
Toronto, M5G 1X5

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Website: Schramek Lab
Publications: Pubmed
Google Scholar: Daniel Schramek
ORCID: 0000-0001-9977-2104
LinkedIn: Daniel Schramek

Accordion Items
  • 2025–present; Professor, Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, Toronto
  • 2024–present; Deputy Director for Discovery Research and Tony Pawson Chair, Sinai Health, Toronto
  • 2022–present; Senior Investigator, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto

Former appointments

  • 2022–2025; Associate Professor, Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, Toronto
  • 2015–2022; Investigator, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto
  • 2015–2022; Assistant Professor, Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, Toronto
  • MSc in Technology Management, New York University, New York, NY, USA; 2012–2014
  • Postdoctoral Fellowship & Emerald Foundation Young Investigator with Dr. Elaine Fuchs, The Rockefeller University & Howard Hughes Medical Institute, New York, NY, USA; 2011–2015
  • PhD, University of Vienna, Vienna, Austria; 2006–2010
  • MSc, University of Vienna, Vienna, Austria; 2000–2006
  • 2024 – Tony Pawson Sinai 100 Chair
  • 2021 – Canadian Research Chair in Functional Cancer Genomics, tier II (renewed)
  • 2020 – ASCINA Award; Austria
  • 2016 – Human Frontier of Science Program (HFSP) Career Development Award
  • 2016 – Early Research Award (ERA), Ontario; Canada
  • 2016 – Susan Komen Career Catalyst Award
  • 2016 – Canadian Research Chair in Functional Cancer Genomics, tier II
  • 2015 – Venture Sinai Scientist Award, Mount Sinai Hospital Foundation, Canada
  • 2015 – CCSDP New PI Award, CIHR-ICR and CCSRI; Canada   
  • 2014 – Regeneron Award for Creative Innovation
  • 2014 – Keystone Future of Science Fund Award, Keystone Symposia; USA
  • 2012 – Human Frontier Science Program (HFSP) long-term postdoctoral fellowship
  • 2012 – Helen Hay Whitney Postdoctoral Fellowship, New York; USA – declined
  • 2012 – Austrian Program for Advanced Research and Technology `APART´ Fellowship
  • 2011–2014 – Young Investigator Award, Emerald Foundation, New York; USA   
  • 2011 – American Association for Cancer Research (AACR) Anna D. Barker Fellowship

Decoding aneuploidy: identifying driver genes and therapeutic targets in recurrent CNAs

The prevalent issue of recurrent Copy Number Alterations (CNAs) across devastating malignancies including breast, lung, brain, HNSCC, and pancreatic cancers is a critical challenge in cancer therapy. While these large-scale genomic gains and losses are common, identifying the specific "driver" genes within these altered regions that fuel cancer progression, and the unique vulnerabilities they create, remains a significant hurdle.

Guided by principles similar to those demonstrated in recent cutting-edge in vivo functional genomics studies, we are employing advanced in vivo gene editing and screening technologies such as CRISPR-KOALA. Our strategy involves systematically dissecting these complex CNA regions directly within physiological models. This allows us to functionally test the contribution of numerous candidate genes located within these amplified or deleted segments.

By doing so, we aim to distinguish true oncogenic drivers from mere passengers and, crucially, to uncover novel, context-specific therapeutic vulnerabilities associated with these recurrent CNAs. This approach allows for a high-throughput, physiologically relevant assessment, moving beyond correlative genomic data to establish causal links. Ultimately, this project seeks to pinpoint robust therapeutic targets within these challenging genomic alterations, paving the way for innovative and more effective targeted treatments for patients suffering from these aggressive cancers.

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Illustration of in vivo gene editing and screening technologies such as CRISPR-KOALA.

Elucidating the landscape of essential genes in various epithelial tissues and under specific oncogenic alterations

Our research is pioneering new frontiers in identifying cancer's Achilles' heels through the development and application of our novel CRISPR-StAR2.0 technology. This cutting-edge platform is specifically engineered to uncover oncogene-specific vulnerabilities - critical dependencies that cancers develop based on the particular oncogenes driving their growth - across a spectrum of malignancies. A major challenge in targeted therapy is understanding how different oncogenes sculpt unique vulnerabilities in diverse tissue environments.

The CRISPR-StAR2.0 system allows us to conduct highly sophisticated functional genomic screens directly in vivo, within physiologically relevant mouse models that accurately recapitulate human cancers in various organs. This powerful approach enables us to systematically perturb genes in the presence of specific oncogenic drivers, precisely mapping out the genetic interactions and dependencies that are essential for tumor survival and progression in a given context. By interrogating these complex biological networks directly in living systems, CRISPR-StAR2.0 overcomes limitations of traditional in vitro screens.

Our goal is to generate a comprehensive atlas of actionable therapeutic targets that are uniquely tailored to cancers driven by distinct oncogenes. This project promises to significantly accelerate the discovery of next-generation precision medicines, offering new hope by exploiting the specific molecular wiring dictated by the oncogenes at the heart of each cancer.

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Illustration of in vitro, in vivo and in GEMM system developed by the Schramek lab to accelerate next-generation precision medicine.

We are always looking for motivated researchers to join our team.

Postdocs: Our research group is always interested in recruiting highly motivated postdoctoral fellows with a strong publication record in cancer biology. Please forward your CV, references and research interests to [email protected].

Graduate students: Our research group is part of the Department of Molecular Genetics at U of T, which has a central admission committee and a rotation system. Graduate students interested in doing a PhD in the laboratory must first be accepted in the Department of Molecular Genetics at U of T.

Notable publications

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Diagram showing how mutant p53 becomes stabilized, how this drives metastasis, and the experimental tools used to identify regulators of p53 stability.
Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability

Molecular Systems Biology, 2024

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Experimental workflow of the in vivo CRISPR screen to identify immune-modulatory cancer genes.
In vivo CRISPR screens reveals SerpinB9 and Adam2 as regulators of immune therapy in lung cancer

Nature Communications, 2023

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Illustration comparing chromatin looping between MYC and the rs55705857 locus in somatic, glioma‑precursor, IDH‑mutant, and IDH‑mutant risk‑allele cells, showing how regulatory interactions change MYC expression.
A non-coding single nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation

Science, 2022

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Illustration of experimental design for in vivo CRISPR screen, showing gene selection from long-tail mutations, intraductal injection of lentiviral libraries and tumor sequencing.
Loss of epigenetic regulation disrupts lineage integrity, reactivates multipotency and promotes breast cancer

Cancer Discovery, 2022

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Diagram showing the workflow for identifying tumor‑suppressor genes in head and neck squamous cell carcinoma.
Rare driver mutations in head and neck squamous cell carcinomas converge on NOTCH signaling

Science, 2020

Join our team

Visit our job board to see research positions.