What I cannot create, I do not understand.
Richard Feynman

Engineering Melanoma Brick by Brick

The development and progression of melanoma is an extraordinarily complex process. Decades of research have revealed dozens of molecular changes and interactions critical for the transition – from point mutations to epigenetic reprogramming to cell-cell interactions. However, no single one of these events provides us with the necessary knowledge to invariably prevent or predict the development of the disease or to abolish it once it has progressed. Our goal is to move toward a complete understanding of human melanoma by engineering its progression in vitro, piece by piece, inside and out, and use this knowledge to drive discoveries in prevention, diagnostics & treatment. Beginning with primary human melanocytes, we strive to engineer both the genetic mutations that drive melanoma and the microenvironment of human skin. We use this system to ask:

  • What is the oncogenic penetrance of each melanoma-associated mutation?
  • Define the factors that drive or stabilize each cell program from normal melanocyte to malignant melanoma, including:
    o Transcription Factors
    o microRNAs
    o Genetic Background
  • Investigate the role of stochasticity and plasticity in melanoma progression

Home

The cells constituting benign nevi and melanomas are defined by both the external microenvironment and internal gene expression, such as the miRNA-regulated networks shown here.


home4

We use a variety of tools, including genome editing, reconstituted skin culture, genetic interaction mapping and holographic imaging.


The Judson lab is currently funded by the Sander Fellows Program, the NIH DP5 Early Independence Award, the UCSF Department of Dermatology, the Helen Diller Family Comprehensive Cancer Center Impact Grant & the Sandler Program for Breakthrough Biomedical Research.

Publications

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Evaluation of Holographic Imaging Cytometer HoloMonitor M4 Motility Applications

Cytometry Part A 2018

Yuntian Zhang, Robert L Judson

Bi-allelic Loss of CDKN2A Initiates Melanoma Invasion via BRN2 Activation

Cancer Cell 2018

Hanlin Zeng, Aparna Jorapur, A Hunter Shain1, Ursula E Lang, Rodrigo Torres, Yuntian Zhang, Andrew S McNeal, Thomas Botton, Jue Lin, Matt...

Genomic and transcriptomic analysis reveals incremental disruption of key signaling pathways during melanoma evolution

Cancer Cell 2018

A Hunter Shain, Nancy M Joseph, Richard Yu, Jamal Benhamida, Shanshan Liu, Tarl Prow, Beth Ruben, Jeffrey North, Laura Pincus, Iwei Yeh, ...

Combined activation of MAP kinase pathway and β-catenin signaling cause deep penetrating nevi.

Nature Communications accepted 2017

Iwei Yeh, Ursula Lang, Emeline Durieux, Meng Kian Tee, Aparna Jorapur, Alan Shain, Veronique Haddad, Daniel Pissaloux, Xu Chen, Lorenzo C...

High accuracy label-free classification of single cell kinetic states from holographic cytometry of human melanoma cells.

Scientific Reports accepted 2017

Miro Hejna, Aparna Jorpaur, Jun Song, Robert L Judson.

CDK1 Inhibition Targets the p53-NOXA-MCL1 Axis, Selectively Kills Embryonic Stem Cells, and Prevents Teratoma Formation

Stem Cell Reports 2015

Noelle E Huskey, Tingxia Guo, Kimberley J Evason, Olga Momcilovic, David Pardo, Katelyn J Creasman, Robert L Judson, Robert Blelloch, Sco...

Two miRNA Clusters Reveal Alternative Paths in Late-Stage Reprogramming

Cell Stem Cell 2014

Ronald J Parchem, Julia Ye, Robert L Judson, Marie F Larussa,Raga Krishnakumar, Amy Blelloch, Michael C Oldham, Robert Blelloch

MicroRNA-based discovery of barriers to dedifferentiation of fibroblasts to pluripotent stem cells

Nature Structural & Molecular Biology 2013

Robert L Judson, Tobias S Greve, Ronald J Parchem, Robert Blelloch

microRNA Control of Mouse and Human Pluripotent Stem Cell Behavior

Annual Review of Cell and Developmental Biology 2013

Tobias S Greve, Robert L Judson, Robert Blelloch

Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells

Nature Biotechnology 2011

Deepa Subramanyam, Samy Lamouille, Robert L Judson, Jason Y Liu, Nathan Bucay, Rik Derynck, Robert Blelloch

miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma

Nature Medicine 2010

Alexander Swarbrick, Susan L Woods, Alexander Shaw, Asha Balakrishnan, Yuwei Phua, Akira Nguyen, Yvan Chanthery, Lionel Lim, Lesley J Ash...

Opposing microRNA families regulate self-renewal in mouse embryonic stem cells

Nature 2010

Collin Melton, Robert L Judson, Robert Blelloch

Embryonic stem cell-specific microRNAs promote induced pluripotency

Nature Biotechnology 2009

Robert L Judson, Joshua E Babiarz, Monica Venere, Robert Blelloch

The GP(Y/F) domain of TF1 integrase multimerizes when present in a fragment, and substitutions in this domain reduce enzymatic activity of the full-length protein

Journal of Biological Chemistry 2008

Hirotaka Ebina, Atreyi Ghatak Chatterjee, Robert L Judson, Henry L Levin

The self primer of the long terminal repeat retrotransposon Tf1 is not removed during reverse transcription.

Journal of Virology 2006

Angela Atwood-Moore, Kenneth Yan, Robert L Judson, Henry L Levin

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