read-more
Read more about Fred Hutch achievements and accolades.
Two postdoctoral researchers at Fred Hutchinson Cancer Research Center are among the 17 early career scientists announced this week as fellows of the Damon Runyon Cancer Research Foundation. Drs. Edie Crosse and Ching-Ho Chang and their fellow honorees across the U.S. will receive four years of funding for their “creative and high-risk projects dedicated to the search for cancer causes, mechanisms, therapies and prevention,” according to the foundation’s announcement.
With her funding, Crosse aims to uncover early mechanisms of the blood cancers known as myelodysplastic syndromes, or MDS, that new drugs could target to prevent disease progression to leukemia. She was sponsored for the award by mentor Dr. Lev Silberstein and co-sponsor Dr. Irwin Bernstein.
Chang, who is mentored by Dr. Harmit Malik, is studying rapidly evolving proteins called protamines that condense DNA within sperm cells. Protamines control how genes are turned on and off within sperm and are also found in many cancer cells.
Each postdoc will receive $231,000 of independent funding to support continued training in their mentors’ labs as they develop their scientific careers.
“We are thrilled to be funding these innovative, young scientists with the brilliance and passion to push boundaries and make breakthroughs,” said Dr. Yung S. Lie, president and CEO of the Damon Runyon Cancer Research Foundation in the award announcement. “They are committed to understanding the fundamental processes driving cancer, which may ultimately lead to new therapeutic approaches for patients. Damon Runyon Fellows are the future leaders of their respective fields.”
Toward new treatments for MDS
MDS, which occur mostly in elderly patients, are initiated in the bone marrow when blood stem cells acquire a genetic mutation that causes them to divide and multiply uncontrollably. Through proliferation and acquisition of further mutations, the disease can evolve into acute myeloid leukemia, for which prognosis and survival rate are very poor.
Crosse aims to identify a specific subset of blood stem cells that are affected by the mutation in the early stages of MDS development. Her goal is to design potential new therapies that inhibit these mechanisms and halt MDS before it fully transforms into leukemia.
“This is an exciting yet ambitious project,” Crosse said. “I’m grateful to the Damon Runyon Foundation for giving me the opportunity to undertake this challenge and for integrating me into a wonderful network of inspiring young scientists in the cancer research field.”
Her mentor Silberstein, who is also a hematologist at Seattle Cancer Care Alliance, said that Crosse’s project is important because it could lead to development of early intervention approaches in blood cancers.
“Understanding early events in leukemia emergence could help us design novel therapeutic strategies which would ‘intercept’ blood stem cells on their journey to become fully leukemic and thus prevent development of this devastating disease,” he said. “Edie proposes to address this question with an incredible precision, at the level of a single cell. With her experience in single cell analysis, developmental biology and stem cell research, she is in a perfect position to succeed.”
Understanding DNA-packaging proteins
Cells use special proteins to help package up their DNA into a tiny amount of space and to regulate how the genetic instructions within the DNA are expressed, or “read” by the cell’s machinery.
While most of our cells use proteins called histones to condense our genomes into the packaged form called chromatin, sperm cells must pack their genomes more tightly. For this, many animals deploy protamines instead of histones. Despite sharing certain functions with the typically slow-evolving histones, protamines have independently arisen in evolution multiple times and are continuing to rapidly evolve.
“I have long been fascinated by this dichotomy, and this fellowship gives me the chance to fully explore this question in the Malik Lab,” said Chang. He is using the fruit fly as a model to study how sperm chromatin regulates gene expression and reproductive fitness, and what happens when these testis-specific proteins appear within cancer cells — a phenomenon that may offer opportunities for the development of new targeted therapies.
“Based on his training and interests, Ching-Ho is ideally suited to understand the mystery of why protamine genes continue to 'break the evolutionary speed limit' in animal genomes,” mentor Malik said. “Ching-Ho has wanted to work on this for a while, but he did not have to work too hard to convince me this would be a fantastic project for him to begin establishing his independent research career. I am especially keen on the unexplored observation that these sperm-restricted genes get mis-expressed in some cancers.”
