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Biomolecular Condensates in Cancer

November 17–20, 2022

Original Dates: January 28–31, 2021


Chaired By

 Danfeng Cai, PhD, Johns Hopkins School of Public Health
 Alex Holehouse, PhD, Washington University in St. Louis
 Tanja Mittag, PhD, St. Jude Children’s Research Hospital


Important Dates

 10/17/2022 -  Travel Form Due
 10/17/2022 -  Abstracts Due


Travel Agent Information

 Meeting #: Refer to your meeting email.
 Hours: 8:00am – 8:00 pm EST M-F
 Domestic: 669-210-8002
 International : 623-516-6140


Venue Information

The Inn at Rancho Sante Fe
5951 Linea Del Cielo
Rancho Santa Fe, CA 92067
858.756.1131

www.theinnatrsf.com


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Program Description

Large-scale cytological changes are a classical hallmark of cancer, although the molecular etiology of these changes has historically been poorly understood. A cell can be organized through membrane-bound organelles such as endoplasmic reticulum and Golgi, or through membrane-less biomolecular condensates such as nuclear bodies and stress granules. While membrane-bound organelles are well-studied, the biology of membrane-less biomolecular condensates is less well-understood. It has recently been found that biomolecular condensates form through phase separation - a demixing phenomenon in which the associated macromolecular components form a dense liquid-like assembly. In addition to large well-defined membrane-less organelles, there exist a growing number of examples in which smaller biomolecular condensates mediate key biological processes. Of particular recent interest, much of the transcriptional machinery appears to consist of biomolecular condensates. The meeting is timely since the field of biomolecular condensates in various aspects of biology has grown exponentially in recent years, and the roles of biomolecular condensates in diseases such as cancer are just beginning to be uncovered.

Misregulation of biomolecular condensates is intimately linked to cancer. For example, both PML bodies and the nucleolus are classic membraneless organelles, and both show massive morphological changes in transformed cells, a result that can now be rationalized in terms of changes to the phase behaviour associated with the underlying components. A number of specific cancers are directly linked to proteins we now know can form biomolecular condensates. The FET family proteins are a collection of RNA binding proteins that contain large unstructured low-complexity domains (LCDs). These LCDs are necessary and su cient to drive phase separation, and in a number of different cancers these LCDs translocate to oncogenic DNA binding domains, driving malignancy. A working model suggests the formation of LCD-mediated assemblies at the associated genetic loci recruits transcriptional machinery, driving unfettered gene expression. While the FET proteins lead to malignancy through oncogenes, cancer-associated mutations in the tumor suppressor SPOP disrupt its normal ability to phase separate, demonstrating that both gain-of-function and loss- of-function mutations are possible.

At the level of gene regulation, super-enhancers are biomolecular condensates that occupy specific loci on the genome and drive high-level constitutive transcription. Recent work suggests that super-enhancers form through phase separation, and that their formation at oncogenes may be a common mechanism through which transcriptional upregulation occurs in transformed cells.

Taken together, there is a growing body of work suggesting biomolecular condensates play strong roles in cancer. This is of particular interest from a therapeutic stand-point as previously ‘untreatable’ malignancy should become vulnerable through a better understanding of the molecular basis of their origins. The goal of this timely Forbeck meeting is to bring together cancer-focused medical scientists, biophysicists and cell biologist in an intimate multi- disciplinary environment to generate ideas on how study of this novel eld can lead to novel treatments for cancer.


Travel Information

Travel forms are due 30 days prior to the start of the meeting to allow enough time to plan transportation.

The San Diego International Airport (SAN) is the preferred airport as it is only 30 minutes from the meeting location.

  • Arrivals - Thursday at 1 PM, 3 PM and 5 PM
  • Departures - Sunday at 10 AM, 12 PM and 2 PM

Submit Travel Form

Abstracts

Abstracts are due 30 days prior to the start of the meeting to allow enough time to prepare the meeting book.

Abstracts should be only one or two paragraphs outlining the theme of your presentation and should reflect the objective and spirit of the meeting (see above). Abstracts will be circulated about one week before the meeting. The meeting organizer will start requesting them a month before the meeting.

Submit Abstract

Forum Participants

Participant Institution
Simon Alberti, PhD Max Plank Institute
Danfeng Cai, PhD Johns Hopkins School of Public Health
Shasha Chong, PhD California Institute of Technology
Jean Gautier, PhD Columbia University
Lin Guo, PhD Jefferson University
Alex Holehouse, PhD Washington University School of Medicine in St. Louis
Isaac Klein, MD, PhD Massachusetts Institute of Technology
Richard Kriwacki, PhD St. Jude Children's Research Hospital
Hyun Lee
Tanja Mittag, PhD St. Jude Children's Research Hospital
Charles Mullighan, MSc, MD St. Jude Children's Research Hospital
Karla Neugebauer, PhD Yale School of Medicine
Miguel N. Rivera, MD Harvard Medical School
Ben Sabari, PhD UT Southwestern
Asmin Tulpule, MD, PhD University of California, San Francisco
Liling Wan, PhD University of Pennsylvania
Ji-Young Youn, PhD University of Toronto
Huaiying Zhang, PhD Carnegie Mellon University

Forum Scholars

Scholar Institution
Jeong Hyun Ahn, PhD University of North Carolina at Chapel Hill
Aravinthkumar Jayabalan, PhD Johns Hopkins University
Hermann Schmidt, PhD Stanford University School of Medicine

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