Head and Neck Cancer

Current Projects
Chao Lu, PhD

Eukaryotic cells develop sophisticated mechanisms to package and access our genetic information. Recent studies have shown that proteins involved in genome regulation are frequently altered in human cancers. These findings agree with laboratory observations that cancer cells often display abnormal nuclear architecture, and raise the questions of whether, and how, aberrant chromatin organization facilitates tumor development. Collectively, Dr. Lu's previous work has identified the molecular mechanisms by which high-frequency mutations in chromatin regulators reprogram genome-wide chemical modifications of DNA and histones. In addition, his work demonstrated that chromatin mutations are pro-oncogenic through the blockade of cellular differentiation. These studies provide compelling evidence for a causal role of chromatin dysregulation in oncogenesis. He proposes a novel pathway of cancer initiation through accumulation of hyper-proliferative and differentiation-refractory tissue progenitor cells driven by epigenome abnormality. His goal is to apply these mechanistic insights to advance current molecular diagnosis, classification and treatment of human cancers.

Project title: "Understanding the mechanism of histone H3 mutation in cancer initiation and maintenance"
Institution: Columbia University
Award Program: Dale Frey Scientist
Cancer Type: Head and Neck Cancer, Sarcoma
Research Area: Chromatin Biology
Luc G. Morris, MD

Head and neck cancer is a lethal malignancy that can arise in the mouth, throat, voice box, and related areas. These tumors are squamous cell cancers that are, in many cases, caused by tobacco use or human papillomavirus (HPV) infection. Head and neck cancers have many molecular similarities with squamous cell cancers of the lung and esophagus. Dr. Morris is studying a poorly understood gene called FAT1, which is frequently altered in head and neck cancer (as well as lung and esophageal cancer). He has found that this gene, in its normal state, prevents tumor development. In this project, he will determine the effects of FAT1 alterations on tumor cell growth, squamous cell development and differentiation, and the clinical prognosis of patients. This work will help to develop new ways of therapeutically targeting the pathways that promote the development of head and neck and other squamous cell cancers.

Project title: "Functionalizing tumor suppressor gene mutations and deletions in head and neck cancer"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Timothy A. Chan, MD, PhD and James Fagin, MD
Cancer Type: Head and Neck Cancer
Research Area: Genomics
Mark G. Shrime MD, MPH, PhD

Mark is a cancer surgeon and health economist. He is examining one of the hidden barriers to surgical oncology access in head and neck cancer—that of non-medical costs. For 81 million people every year, surgery leads to catastrophic impoverishment, but only 40% of that is due to the direct medical costs of surgery. The rest is due to the hidden costs of transportation, food, and lodging necessary to get surgery. He proposes to design and optimize a cash transfer for patients with head and neck tumors in a low-income West African country. The effects of this cash transfer on surgical oncology utilization will then be tested in a randomized, controlled trial. These findings could apply globally to improve access to cancer care. Dr. Shrime works under the mentorship of John G. Meara, MD, DMD, MBA, at Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.

Project title: Cash transfers for cancer surgery in West Africa: their health and economic consequences
Institution: Massachusetts Eye and Ear Infirmary
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): John G. Meara, MD, DMD, MBA
Cancer Type: Head and Neck Cancer
Research Area: Surgical Oncology
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