Tracking an Elusive Foe: Cancer Research at The Jackson Laboratory
Many of The Jackson Laboratory’s principal investigators are immersed in the basic research essential to clinical cures for cancer in its many forms. These researchers’ collective goal is to better understand the complex genetic and biological factors that contribute to the uncontrolled growth and spread of abnormal cancer cells. Their work is driving development of new and better clinical strategies for preventing, detecting and eradicating cancer.
The Jackson Laboratory was founded to explore the idea that cancer is not contagious, but genetic, and that susceptibility to cancer is linked to heredity. As a National Cancer Institute-designated Cancer Center, The Jackson Laboratory is an essential part of the genetics revolution that is transforming cancer research and treatment.
Unraveling the complexities of genetics and cancer
Scientists at The Jackson Laboratory are working to provide doctors with the tools they need to treat cancer at its earliest stages—or even prevent the disease.
The Jackson Laboratory’s cancer research involves the cooperative efforts of both new and veteran principal investigators. They include Ph.D.s Carol Bult, Gary Churchill, Kevin Mills, Lindsay Shopland, Lenny Shultz and Kyuson Yun. This cancer research “brain trust” continues to expand, most recently with the recruitment of Ph.D.s Richard Maser and Chengkai Dai, who is also a physician.
Each of these principal investigators is exploring a different aspect of the molecular mechanics and microanatomy of cancer cells and tumor behaviors. Collectively, these researchers and their colleagues are contributing to a better understanding of how the interactions of anatomy, physiology and biochemistry make cancer among the most complex of genetic diseases.
Stress response in cancer cells
Dr. Chengkai Dai’s research looks at cancer from a whole new angle. Dai is among the first cancer researchers to study the stress response, a mechanism found throughout nature that normally protects healthy cells from environmental stress.
In human cancers, the system, in effect, change allegiance and instead helps to protect cancer cells, allowing them to grow and divide very rapidly. Recently awarded a $2.7 million grant through the National Institutes of Health’s New Innovators Award program, Dai is looking at ways to short-circuit the stress response in cancer cells, which provides a new and promising way kill the cancer cells and develop effective treatments.
Exploring the structure of the human genome
Lindsay Shopland is going beyond the DNA sequence, the letters that make up the DNA code. Her research aims to unravel the three-dimensional physical structure of the human genome and how it can contribute to the onset of cancer.
DNA is tightly packed into the nucleus in a very convoluted yet precise arrangement. Shopland’s research team is exploring the structure of the human genome and how variations can help determine individual susceptibility to cancer. These studies are helping to shed new light on how gene regulation can go wrong in cancer and other human genetic diseases.
Understanding cancer stem cells
Kyuson Yun and her research team focus on understanding the regulation of stem cells, including stem cells associated with cancer. These cancer stem cells have been only recently discovered and characterized. They are thought to be significant players in cancer initiation and maintenance. Just as normal stem cells develop into different types of cells that make up a healthy body, cancer stem cells give rise to all the other cell types found in cancer.
Yun’s research is identifying cell factors that control stem cell development and behavior in both normal and cancer stem cells. Cancer stem cells are thought to evade many chemotherapeutic regimens and cause recurrence, so finding their weaknesses is vital to developing better cancer therapies.
The Mouse Tumor Database at the Jackson Laboratory
Carol Bult oversees a research team that maintains the Mouse Tumor Database, the most comprehensive publicly accessible database on cancer characteristics in strains of mice most useful for cancer research. Bult is also exploring the genetic basis of lung cancer, the leading cause of cancer deaths worldwide. Her team’s work involves evaluating how genes and networks of genes behave in human lung cancer tumors, using lung cancer tissue samples being provided by hospitals throughout Maine.
The Bult lab is working in collaboration with researchers at Children's Hospital Boston to better understand normal lung development as a framework for identifying key genes and pathways in lung cancer.
The function of telomeres in cancer development
Rick Maser studies what happens at the end of chromosomes, the structures that contain the linear threads of DNA that encode all of our genes. Like the protective plastic tips on the ends of shoelaces, each of our 46 chromosomes has specialized components at each end that keep them from fraying or unraveling. Called telomeres, the components are vital to proper cell division, but over time they erode. Too much erosion leads to damage to the rest of the chromosomes, which can play a role in cancer and aging.
Maser’s lab is investigating how normal telomere maintenance impacts both cancer and the normal aging process. He is also seeking to understand what happens when telomere function is disrupted, particularly how it can lead to the beginning of cancer in various tissues.
Studying DNA repair mechanisms
We have huge amounts of DNA, and it is assembled in fragile and very complicated structures. Kevin Mills and his team are studying how the body keeps the structures stable and how DNA is repaired when damage occurs. Such damage includes translocations, the exchange of genetic material between chromosomes that can trigger tumor initiation and growth. Understanding DNA repair mechanisms is contributing new insights into the molecular mechanics of cancer and therapeutic targets. Manipulation of natural damage and repair mechanisms may provide new ways to provoke cancer cell death.
The Mills lab is also working on finding markers in DNA that detect cancer at very early stages. The goal is to find cancerous cells quickly enough that treatment can begin before a patient becomes ill.
Modeling human genetics in the laboratory
Lenny Shultz has spent decades in research that has led him to genetically engineer a mouse model capable of hosting living human cancer cells. The genetics of a mouse is similar to the genetics of humans. That makes mice the ideal model for exploring how to prevent, control and cure human cancers.
Shultz made possible the ability to graft human cancer cells into mice with suppressed immune systems. This allows cancer researchers to study the process in vivo—in life—as they determine why cancer wreaks havoc on otherwise healthy organ systems. This is research that cannot be pursued with humans. The bottom line is that Shultz’s unique mice provide insights into living human biology that aren’t otherwise possible.
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Scientists at The Jackson Laboratory are developing new genetic and genomic research capabilities to delve into the root causes of cancer.
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