September Newsletter

MDS PROGRAMS

E.P. Evans MDS Center Hematological Malignancies Seminar Series:

“Decoding cancer via giant cells: Toward a unified understanding of embryogenesis and tumorigenesis at an organism level”

Jinsong Liu MD/PhD

Professor

Department of Anatomic Pathology

University of Texas MD Anderson Cancer Center

Date: Wednesday, October 04

Time: 12:00PM

Location: ICRC first floor auditorium

Hosted By: Azra Raza, M.D

“Genetic Predisposition to Myeloid Malignancy.”

Akiko Shimamura, MD, PhD

Professor, Pediatrics, Harvard Medical School

Director, Bone Marrow Failure and MDS Program, Dana Farber/Boston Children’s Cancer and Blood Disorders Center

Date: Wednesday, October 25

Time: 12:00PM

Location: ICRC first floor auditorium

Hosted By: Lei Ding, PhD

Other Seminars of Interest;

“Multi-Cancer Early Detection - Novel Approaches and Public Health Impact”

Joshua J. Ofman, MD, MSHS

President, GRAIL LLC, an Illumina Company, Menlo Park, CA

Date: Wednesday, December 7

Time: 4:00 PM

Location: ICRC 1st Floor Auditorium

For more info: rk3244@cumc.columbia.edu

MDS Faculty Meeting:

Date: Tuesday, September 19

Time: 12:00PM to 1:30PM

Location: Black Building, Conference Room 1418

E.P. Evans MDS Center Trainees Workshop Series Presentations

Date: Wednesday, September 27

Time: 12:00 PM to 1:30PM

Location: Black Building room 1418

Pizza & refreshments provided

MEMBER ANNOUNCEMENTS

Exciting publications, announcements and job opportunities from the MDS Full & Affiliate member labs.

Winning Pilot Awards

“Predicting AML by Means of m6A and YTHDF Proteins Activity”

Lead Investigator: Sara Zaccara, PhD, assistant professor, Department of Systems Biology

For decades, it was believed that information in messenger RNA (mRNA) was confined to its nucleotide sequence. However, new methods to study mRNA have shown it contains additional information in the form of chemical modifications. The most common of these modifications is called N6-methyladenosine (m6A) and Dr. Zaccara’s past research has shown that AML depends on m6A in order to develop. Currently it is unknown whether the events that cause m6A and other chemical modifications could be used as a diagnostic tool for detecting the earliest stages of AML. Dr. Zaccara’s pilot project hopes to identify whether m6A could be considered a biomarker of MDS progression to AML and understand mechanisms underlying m6A regulation during that progression. Overall, these studies have the potential to fundamentally change the current view of how m6A functions during AML progression and provide alternative therapeutic avenues for AML treatment.

“Nucleolar Dysfunction as a Therapeutic Liability in Cohesin Mutant MDS”

Lead Investigator: Aaron Viny, MD, assistant professor of medicine, Department of Medicine and Columbia Stem Cell Initiative

Co-Investigator: Hans Scnoek Willem, MD, PhD, Byron M. Thomason professor of medicine (in Microbiology and Immunology)

The genes that control gene expression are frequently mutated in blood cancers. STAG2 is a gene that helps control DNA organization within the nucleus and is recurrently mutated in MDS. Dr. Viny's lab has observed that mutations cause fragmentation in the nucleus in MDS patient bone marrow cells and genetically engineered mouse models. This project hypothesizes that STAG2 mutations induce stress in the nucleus as a result of the loss of rDNA loop structure. In this proposal, Dr. Viny and collaborators will test the hypothesis that nucleolar stress in mutant AML represents a mutation-specific therapeutic liability and investigate the role of nucleolar dysfunction.

Winning Fellowships

“Modeling Human Clonal Hematopoiesis of Indeterminate Potential (CHIP), MDS, and AML Using in Vitro Hematopoiesis from Gene-Edited Induced Pluripotent Stem Cells”

Lead Investigator: Yong-Oon Ahn, PhD, associate research scientist

In elderly individuals, a process known as clonal hematopoiesis of indeterminate potential (CHIP) occurs, in which hematopoietic stem cells (HSCs) multiply, creating clones with mutations. These mutations can lead to MDS, and even further mutations can progress the condition to AML. This study utilizes induced pluripotent stem cells (iPSCs), which are cells derived from healthy donors or patients and used to study cancer and other diseases. Using iPSCs, Dr. Ahn plans to model the clonal evolution that occurs during CHIP and its progression to MDS and AML. The iPSCs used will be genetically modified and then differentiated into HSCs, myeloid, and NK cells, and single-cell analysis will be conducted to understand each cells’ growth and transformation to explore potential treatments for MDS/AML.

“Investigate the Impact of Genotoxic Therapies on rDNA Instability at the Single Cell Level and Its Role in Therapy-Induced MDS/AML”

Lead Investigator: Xiaolu Zhu, PhD, post-doctoral research scientist

Co-Investigator: Shan Zha, MD, PhD, professor of pathology and cell biology, Institute for Cancer Genetics; professor of microbiology and immunology, Herbert Irving Comprehensive Cancer Center; James A. Wolff professor of pediatrics, Department of Pediatrics

Therapy-related MDS (t-MDS) is a late and aggressive complication of anti-cancer treatments with a dismal prognosis. t-MDS is caused by DNA damage or selection that occurs as a side-effect of chemotherapy. Although there is a general connection between accumulative DNA damage and the development of MDS, the exact type of damage and genomic elements involved in MDS's development remain unknown. Dr. Zhu and colleagues have recently developed several new tools to assess genomic instability in ribosomal DNA (rDNA). During their fellowship, Dr. Zhu will address why specific genotoxic agents, but not others, pose a high risk for t-MDS and the repair pathways, and investigate the mechanism that suppresses rDNA instability.

Azra Raza, MD, and Abdullah Ali, PhD, Receive Funding to Develop Drug Discovery Platform

With funding from TFC Therapeutics, Dr. Raza and Dr. Ali will focus on developing new strategies to target tumor macrophage hybrid cells in order to prevent cancer metastasis and overcome resistance to traditional cancer therapies.

Other Events

MDS Foundation: Move for MDS: New York City

Join New York City's Move for MDS community walk and move the fight against Myelodysplastic Syndromes forward.

https://secure.qgiv.com/event/23moveformdsnewyorkcity/

HICCC PROGRAMS

Filippo Giancotti, MD PhD Cancer Metastasis Symposium

Tuesday, September 12, 2023

9:00 AM to 6:30 PM

The HICCC is hosting a special symposium focused on cancer metastasis. Th epurpose is to increase our understanding of the mechanisms of cancer metastasis and to translate the findings into novel therapies for advanced stage cancers. This symposium owill honor the late Filippo Giancotti, MD PhD, a leader in the field. For more information, a link is provided below.

https://events.columbia.edu/cal/event/eventView.do?b=de&calPath=%2Fpublic%2Fcals%2FMainCal&guid=CAL-00bbdb71-89913ff4-0189-93aa02b3-00003fe4events@columbia.edu&recurrenceId=

HICCC Seminar Series - Distinguished Speaker

Wednesday, September 20, 2023

4:00 PM to 5:00 PM

Michael B. astan, MD, PhD Executive Director, Duke Cancer Institute William and Jane Shingleton Professor, Pharmacology and Cancer Biology Professor of Pediatrics, Duke University School of Medicine

Title: “DNA Damage Responses: Bedside to Bench to Bedside”

Thursday, September 21, 2023

12:00 PM to 1:00 PM

Sita Kugel, PhD Assistant Professor, Human Biology Division and Deputy Co-Director of the Pancreatic Cancer Program at the Fred Hutch Cancer Center

Title: "Subtype-specific vulnerabilities in GI cancers”

HICCC Scientific Seminar

Monday, September 25, 2023

12:00 PM to 1:00 PM

Sakari Vanharanta Ph.D Sigrid Jusélius Professor in basic medicine University of Helsinki

Title: Deconstructing tissue-specific mechanisms of carcinogenesis