Damon Runyon News

Dr. Li focuses on how cells become cancerous when they have an abnormal number of chromosomes or broken parts of a chromosome. The centromere, which joins two arms of a chromosome, is essential for faithful chromosome segregation during cell division and genome stability. When chromosomes fail to be delivered correctly to each new cell, the abnormal chromosomes may form “neocentromeres” which have been discovered in developmental disorders and cancer. Dr.

Dr. Guiley [HHMI Fellow] is focusing on the tumor suppressor protein p53, which is inactivated in half of all cancers, making it the most frequently mutated gene in cancer patients. Normally, when DNA is damaged, p53 stops cell division to allow the cell to repair acquired mutations. Without this safety measure, cells continue to divide and become cancerous. Dr. Guiley aims to develop a novel small molecule drug approach to target a common mutation in p53 and restore its function. These studies have the potential to benefit patients with many different types of cancer.

Dr. Duffy is investigating how neuronal activity can regulate gene expression through a potentially novel mechanism in the developing brain, called RNA turnover. This mechanism may enable gene expression to be rapidly and locally controlled at individual connections between neurons based on neuronal activity. There is evidence that neuronal activity may contribute to pediatric malignant glioma brain tumors. Dr. Duffy aims to characterize this process and identify new therapeutic targets for pediatric brain cancer.

Dr. Crossley [AGBT-Elaine R. Mardis Fellowship in Cancer Genomics] is developing reaction-based chemistry to address the problem of “undruggable” targets in cancer therapy. These proteins lack grooves or “pockets” on the surface that can potentially bind small molecule drugs. A small molecule that can react with an amino acid in the target protein, forming a covalent bond, may circumvent the problem of poor binding pockets. Dr.

Dr. Chen is creating the molecular language of cell signaling from the bottom up. Intra- or extra-cellular signals vary continuously and are often interpreted combinatorially in cells. Neural networks in biology and computer science offer a powerful way to interpret signal combinations. Dr. Chen will combine protein design and synthetic biology approaches to build a protein-based cellular circuit that can sense multiple inputs and carry out diverse functions based on pre-programmed instructions.

Dr. Branon is exploring the relationship between the human body and the microbes that inhabit the gut, which affects physiology, development and disease. Recently, scientists discovered that cancer patients with a greater abundance of the bacteria Akkermansia muciniphila in their guts respond better to checkpoint inhibitor immunotherapies. Dr. Branon is using transcriptomic and metabolic profiling, as well as genetic manipulation of both the host and microbe, to elucidate the molecular interactions that underlie this protective effect.

Dr. Sparks is investigating the cellular machinery that carries out DNA replication and how this process can go awry in cancer cells. Specifically, he is focusing on the eukaryotic replisome, which is a complex of enzymes that helps cellular DNA replicate during cell division. He has found that the replisome can overcome bulky obstacles on a DNA strand, such as DNA-protein cross-links (DPCs), during replication to maintain genome integrity. DPCs, generated from cellular metabolites and environmental mutagens, are likely important for cancer etiology.

Dr. Russell is investigating the mechanisms by which immune cells recognize influenza infection. Yearly influenza epidemics threaten immunocompromised individuals, including cancer patients, who are at an increased risk of complications following infection. His research combines virology, single-cell transcriptomic approaches, and computational biology to study innate immunity to viruses. Specifically, he aims to address the question of why immune responses to different influenza pandemics have differed so much-exploring why some strains are more or less immunogenic.

Dr. Kalish is studying a rare hereditary syndrome called Beckwith-Wiedemann syndrome (BWS), which increases the risk of children developing kidney and liver cancers. These individuals have epigenetic changes on chromosome 11 that are found in other types of cancers. Epigenetic markers modify DNA so gene expression is turned on or off; changes in this process can cause cancer. By understanding how cancer is triggered in BWS, Dr.

Basal cell cancer (BCC) is the most common cancer in the United States with 2 million cases annually resulting in $5 billion in societal cost. Although the majority of BCCs are small and surgically accessible, some individuals develop frequent recurrences of BCC and suffer from severe disability related to surgery and decreased quality of life. Dr. Sarin [D.G. 'Mitch' Mitchell Clinical Investigator] will focus on a group of 100 patients who develop extreme numbers of this skin lesion, in order to identify the genetic mechanisms that contribute to cancer susceptibility.