Dynamic Histone Methylation and Chromatin Organization in Tumor Suppression
Forum Chairs
Forum Description
A multitude of activities and functions have arisen around the enzymes that provide specific methylation marks on histones, and which are perturbed in cancer. These enzymes, for example SETD2, are no longer considered as simple factors in the specificities of methylation. Recent data suggests that spatial distribution, dynamic activity, structural composition, as well as non-histone targets adds to the complexity of these interactions as they pertain to cancer. The recent explosion of mutations in the histone tail residues as well as methyltransferase domain mutants has led to potential for siloing as the field grapples with the diverse functions of these proteins. A meeting of this nature has potential to advance the science of histone biology in cancer suppression and to bridge in the many additional targets and factors involved, bringing investigators approaching this problem from a diverse array of angles.
Forum Summary
A few years delayed, but the issue remained: how do enzymes that modify histones contribute to cancer, and can we apply that knowledge to better understand mechanisms of tumorigenesis or to develop therapies?
Gathered in a remote part of Tennessee, at a lovely secluded historic mill and resort, complete with a hike to a massive waterfall, we wrestled with topics that discretely play out in our cells every minute. We opted to have an entirely in-person meeting, thinking that the in-person engagement would be the most effective. With a few last-minute cancelations due to COVID travel issues, we were able to add several early career faculty guests whose work was complementary; their presence in fact made the program truly outstanding. The success of a Forbeck Forum comes down to three things: 1) An engaged set of participants who are engrossed in the topic during the sessions and in between—at meals, while hiking, in the evening when socializing, 2) A topic that has a lot of facets that are relevant to human physiology and cancer, and a group willing to approach with openness—an open mind to consider outside the box concepts, and openness to share opinions, ideas, and expertise, and 3) A cohort of early career researchers who are energized, excited for the future, and enthusiastic about the careers they are launching into—and the community of investigators that they are joining.
The meeting was launched by co-chair Brian Strahl, PhD, an original discoverer of the histone code, showcasing a new function for histone methyltransferase, SETD2, as a structural element interacting with nuclear features independent of its well-known catalytic function “writing” trimethylation on histone H3, lysine 36 (H3K36). SETD2 was a popular enzyme in this forum, and its varied activities emerged as a theme of the meeting, as well as its potential for therapeutic targeting vs acting as a major guardian of the cell. Histone marks such as the one laid down by SETD2, are interpreted by a variety of “reader” molecules, and Mark Bedford, PhD, revealed potential for many new readers that may interpret histone methylation by H3K36 enzymes. These epigenetic marks maintain the genome, until portions of the genome are aberrantly activated, a process important in overlapping functions between viral response and cancer, as detailed by scholar Charles Isak, PhD. We learned intricate details of the interactions between marks shared and exclusive to histones and nucleosome by Nick Young, PhD. Matthew Lorincz, PhD, shared critical information on the delicate orchestration of these marks in determining cell identities and fates. Scholar Michael Meers, PhD, introduced the concept that transcription factors might take advantage of epigenetic changes, functionally “highjacking” the genome. Our first day was concluded with a return to SETD2, and Jerry Workman, PhD, sharing insights into the domain specificity of this multifunctional protein. On day two, we learned from Frank Mason, PhD, that when SETD2 is deleted, as occurs in a variety of cancers, that its loss leads to the loss of genomic integrity. Additional insight by co-chair Kimryn Rathmell, MD, PhD showed that SETD2 functions in the non-genic space and its loss further contributes to the phenotype of cancer cells. Noncanonical targets in the cell, namely the cytoskeleton, were discussed by Cheryl Walker, PhD, as a further source of genomic instability. Factors regulating SETD2 itself were discussed by Ruhee Dere, PhD. Two talks on strategies to pharmacologically take advantage of vulnerabilities placed by SETD2 loss were presented by scholars Aguirre de Cubas, PhD, and Josh Jang, PhD. Or Gozani, MD, PhD, shared mechanisms that cancer cells use to amplify enzymes in this pathway, and Tatiana Kutateladze, PhD, took us on a tour of the detailed structural domains of proteins regulating and reading histone methylation. Finally, Peter Lewis, PhD, used mutations found in cancers that alter the histones themselves to teach us more about the interactions and regional specificity of these histone marks that brought us full circle. There are opportunities to use the histone code to understand the cellular protections that prevent cancer, and key vulnerabilities that we explored as future therapeutics when those protection are disrupted. There are functions that are contentious, and more remaining to be discovered, as we seek to understand this process as it relates to human cancer.
Venue & Travel Information
Travel Forms
Travel forms are due 30 days prior to the start of the forum to allow enough time to plan transportation.
Nashville's International Airport (BNA) is the preferred airport as it is only 60 minutes from the venue.
- Arrival day of the forum at approximately 1:00 PM and 4:00 PM
- Departures from the venue at approximately 8:00 AM and 12:00 PM
Travel Policy
Please familiarize yourself with our policies and procedures for travel. We truly appreciate you taking the time to participate in this forum. As you make your plans, please remember that we are a nonprofit organization dependent on donations and volunteers. We do NOT pay for upgrades, change fees, incurred costs resulting from a flight change, transportation to or from your local (home side) airport, meals or other incidentals.
- Travel Confirmation will be sent out within 1 week of the forum. This will include a hotel confirmation number, if there is one, and airport transfer details. We have to wait until we receive almost everyone’s travel to book airport transfer. Due to frequent airline changes, we wait until the week of the forum to send this out.
- Airport transfer is provided by Foundation staff, volunteers or arranged shuttle at specific times. If you opt to utilize Foundation airport transportation on your travel form, please be patient in receiving this information. We will send it to the week of the forum.
- Speaker agenda is not sent out prior to the forum. It will be provided upon arrival in the forum packet. We do not tell people when they are speaking because we expect everyone to attend all sessions. Sessions are all day Friday and Saturday.
- REMINDER: We do not reimburse for home side airport transfer or incidentals while traveling. We will not honor miscellaneous receipts sent for these expenses.
- Spouses are welcome to come with you at their own cost but are not allowed to attend the forum. Please no children.
What the Foundation Pays
Accommodations and meals are provided by the foundation during the forum. Airfare will be covered only if booked through our travel agent. The Foundation will also cover airport transportation on the forum side at the designated shuttle times. You can select not to utilize Foundation arranged transportation at your own expense when completing the travel form. Once your travel form is received your accommodations and airport transfer will be confirmed. Please let us know of any food allergies or other information we should be aware of on the travel forms.
- If you would like your airfare covered by the Foundation, you must book with our travel agent. Note we do not cover upgrades, changes, late bookings, etc.
- Flights must be booked at least 30 days prior to the forum to confirm your accommodations and airport transfer.
- As a nonprofit we utilize volunteers and other methods to maximize our efforts (or our donor support) when making accommodations and arranging ground transportation. Ground transportation will be provided upon your arrival either by a foundation volunteer or arranged shuttle. You will be provided airport transportation information the week of the forum. We do not reimburse for home side airport transfer or incidentals while traveling.
Abstracts
Abstracts are due 30 days prior to the start of the meeting to allow enough time to prepare the meeting book.
The 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.
Forum Structure
The structure of the forum has been developed over years of experience.
- Participants have approximately 45 minutes, depending on the number of participants, for their presentation and discussion. The presentation is meant as a conversation start and should last about twenty minutes briefly covering background information and areas that are new or need further input. This should be structured in such a way as to lead to a lively discussion. Participants are encouraged to interrupt to ask questions or start discussions.
- A MAXIMUM of 5 slide equivalents per presentation is allowed (Power point slides should not contain more than one graph or gel per slide and no more than 5 bullet points to stress the points being made by the presenter.) We appreciate cooperation with the spirit of this guideline. Handouts are welcome but should be distributed before sessions.
- Everyone is expected to actively participate in every session and discussions.
- The time spent at the forum is relatively short, so please be familiar with papers received prior to arrival.
- It is very important that you commit to all sessions of the 2 days of the forum.
Forbeck Scholars Participation
Scholars are selected for each Forbeck Forum. These are outstanding junior clinical or post-doctoral fellows selected based on the quality and relevance of science.
- Scholars present for 30-45 minutes, depending on the number of participants
- The same presentation rules apply for scholars
- After the Forum you are selected to attend, you will attend three years of Scholar Retreats held in Lake Geneva, WI. If you attend a Fall Forum, you will attend the Spring Retreat. If you attend a Spring Forum you will attend a Fall Retreat.
- Scholars are selected by the Foundation Scientific Advisory Board and peer reviewers selected from past Forbeck Scholars.
General Program
The outline below illustrates a typical program schedule. You will receive a complete schedule, including speaking times, the Thursday the forum starts.
Frequently Asked Questions
Below are some of our most Frequently Asked Questions. If you have something new to ask, please feel free to contact us.
- Travel Confirmation will be sent out within 1 week of the forum. This will include a hotel confirmation number, if there is one, and airport transfer details. We have to wait until we receive almost everyone’s travel to book airport transfer. Due to frequent airline changes, we wait until the week of the meeting to send this out.
- Airport transfer is provided by Foundation staff, volunteers or arranged shuttle at specific times. If you opt to utilize Foundation airport transportation on your travel form, please be patient in receiving this information. We will send it to the week of the forum.
- Speaker agenda is not sent out prior to the meeting. It will be provided upon arrival in the meeting packet. We do not tell people when they are speaking because we expect everyone to attend all sessions. Sessions are all day.
- Frequently airport transfer is provided by volunteers. Please be patient on receiving this information. Airport transfer will be sent out prior to arrival.
- REMINDER: We do not reimburse for home side airport transfer or incidentals while traveling. We will not honor miscellaneous receipts sent for these expenses.