The Gene Regulation & Cell Proliferation Program is an interdisciplinary effort focused on understanding the mechanisms that govern both normal and cancerous cell growth. The researchers in this program combine traditional experimental biology with cutting-edge technology to gain significant insights into DNA replication, epigenetics, and RNA biology.
Research in the Gene Regulation and Cell Proliferation program explores how these cellular processes drive the pathogenesis of human cancer. Scientists in this Program have identified numerous epigenetic vulnerabilities in aggressive cancers. The Program has also discovered aberrantly expressed non-coding RNAs and splicing alterations that provide the rationale for a potential new class of cancer therapeutics. In addition, significant advances have been made in our understanding of the mechanisms and regulation of DNA replication.
The Program is increasingly extending its studies to single cell biology and cancer metabolism, in an effort to understand the complexity and diversity of tumor cell types. There are numerous interactions among Program members and clinical researchers both locally and around the world. As a result, researchers in the Gene Regulation and Cell Proliferation Program continue to make seminal discoveries about the mechanisms that govern cell proliferation.
Christina Renna Foundation raises $30,000 for continuing pediatric cancer research at CSHL
January 22, 2018
The Christina Renna Foundation presented $30,000 to Cold Spring Harbor Laboratory (CSHL) at its 11th annual Angel’s Wish Gala held on January 20, 2018. These funds will support the Sarcoma Research Project, which focuses on a rare and often fatal cancer, rhabdomyosarcoma (RMS). Associate Professor Christopher Vakoc of CSHL was awarded the 2018 Christina Renna...
Molecular decoy helps researchers halt and reverse acute leukemia in mice
January 8, 2018
Cold Spring Harbor, NY — Cancer researchers today announced they have developed a way of sidelining one of the most dangerous “bad actors” in leukemia. Their approach depends on throwing a molecular wrench into the gears of an important machine that sets genes into motion, enabling cancer cells to proliferate. In tests in mice, the...
David Spector is named ASCB Fellow
December 11, 2017
David L. Spector, Ph.D., a professor at Cold Spring Harbor Laboratory (CSHL) and the Laboratory’s Director of Research, was named a fellow of The American Society for Cell Biology (ASCB). “This is a great honor, as the ASCB is the premiere society promoting scientific research, diversity in science, and advocating for public policy that impacts...
Research profile: Leemor Joshua-Tor
November 27, 2017
When she was in the 7th grade, Leemor Joshua-Tor came upon a fragrant box that once held her mother’s perfume. It proved the perfect container for a set of flash cards that she was using to learn properties of the chemical elements. “I think my brain connected doing chemistry to good feelings, good smells,” she...
Friends of T.J. present $50,000 gift for ongoing rhabdomyosarcoma research
November 7, 2017
Cold Spring Harbor, N.Y. — On November 1st, The Friends of T.J. Foundation presented CSHL Associate Professor Chris Vakoc with a check for $50,000 for his ongoing rhabdomysarcoma (RMS) research. Dr. Vakoc heads the RMS research initiative at Cold Spring Harbor Laboratory. The Friends of T.J. Foundation is one of a group of local funders...
Cryo-EM imaging suggests how the double helix separates during replication
October 23, 2017
Cold Spring Harbor, NY — Life would be impossible if the DNA in dividing cells were replicated with anything less than near-perfect precision. Every time a nucleated cell commits to becoming two cells, every “letter” of its genome must be replicated once and only once. In humans, the task boggles the imagination. If unwound, the...
Halfway around the world, a reunion of friends opens door to a cancer discovery
August 31, 2017
LabDish blog After interviewing for a position in a pancreatic cancer lab at Cold Spring Harbor Laboratory, 7,000 miles from his hometown in South Korea, Chang-il Hwang did what many of us would: he posted about it on Facebook. Little did he know that he was rekindling a friendship that would pave the way to...
Structural view suggests RNAi machinery multiplies its efficiency in repressing gene expression
August 3, 2017
Cold Spring Harbor, NY — Continuously throughout our lives, our cells are expressing genes. It’s the first step in making proteins, the stuff of all the structures in the body and molecular players in the countless dramas unfolding every second as cells execute tasks that enable our organs to function. Many specialized and overlapping mechanisms...
Long-sought mechanism of metastasis is discovered in pancreatic cancer
July 27, 2017
An epigenetic factor reprograms gene enhancers, enabling cancer cells to “remember” an earlier developmental state Cold Spring Harbor, NY — Cells, just like people, have memories. They retain molecular markers that at the beginning of their existence helped guide their development. Cells that become cancerous may be making use of these early memories to power...
Freeze-frames of enzymes in action have implications for a new cancer treatment concept
July 3, 2017
Tutases are a class of enzymes that regulate the microRNA let-7—a gene that is commonly downregulated in cancers. The Joshua-Tor lab used x-ray crystallography to capture images of the enzyme in action, offering insight into how these potential cancer targets function.
Newly identified small RNA fragments defend the genome when it’s ‘naked’
June 29, 2017
Fragments snipped from tRNAs protect embryonic stem cells while they’re being epigenetically reprogrammed Cold Spring Harbor, NY — Our genomes are minefields, studded with potentially damaging DNA sequences over which hundreds of thousands of sentries stand guard. These sentries, called epigenetic marks, attach to the double helix at such spots and prevent the underlying DNA...
A protein that stem cells require could be a target in killing breast cancer cells
June 1, 2017
Cold Spring Harbor, NY — For years, cancer experts have realized that cancerous cells behave in certain ways like stem cells, unspecialized cells that when exposed to certain signals, can “differentiate.” When a stem cell differentiates, it starts down a one-way path that will result in its specialization and eventually its death. For instance, a...
Redefining biologists, redefining genes
May 16, 2017
Base Pairs podcast Set aside your notions of how biologists are born, or what the word “gene” means as you listen to our first chat episode. We talk with Assistant Professor Molly Hammell, a genome biologist who started out as an astrophysicist. She tells us what it’s like to peer deep into space using a...
CSHL’s Dr. Leemor Joshua-Tor is elected to The National Academy of Sciences
May 2, 2017
Washington, D.C. and Cold Spring Harbor, NY — Cold Spring Harbor Laboratory Professor Leemor Joshua-Tor, Ph.D., a structural biologist whose work is known and respected worldwide, has been elected to The National Academy of Sciences (NAS). Dr. Joshua-Tor, who since 2008 has been an Investigator of the Howard Hughes Medical Institute, joins a new class whose...
Dark matter of the genome, part 2
April 15, 2017
Base Pairs podcast Did you know? If unwound and tied together, the strands of DNA in one cell would stretch past the entire length of you body (~ 6 ft). Now imagine that among all that, only enough genetic information to run the length of your thumb-nail is of any importance! Soon after the Human...
CSHL’s Dr. Leemor Joshua-Tor Elected to American Academy of Arts and Sciences
April 14, 2017
Cambridge, MA and Cold Spring Harbor, NY — Professor Leemor Joshua-Tor, Ph.D., of Cold Spring Harbor Laboratory is among 228 newly elected members of The American Academy of Arts and Sciences, it was announced today. Dr. Joshua-Tor is a Howard Hughes Medical Institute Investigator. The new class of Academy members will be inducted at a ceremony...
Protein complex that takes first steps in human DNA replication dance is captured at high atomic resolution
March 16, 2017
The Stillman and Joshua-Tor labs collaborated to obtain the structure of the active human Origin Recognition Complex (ORC), the proteins that control the initiation of DNA replication. Using both cyro-EM and x-ray crystallography, the labs obtained a high-resolution image of the ORC proteins bound to DNA, providing insights into the most fundamental process in cell proliferation.
Focus on quiescent cells brings to light the essential role of RNA interference in transcription control
November 9, 2016
Cancer forms when quiescent cells begin dividing and proliferating. New research from the Martienssen lab demonstrates that the RNAi machinery—which is often mutated in cancers—plays a key role in this transition, holding cells in quiescence.
Non-coding portions of genome are found to play role in cancer
September 27, 2016
CSHL scientists test an antisense method of targeting long noncoding RNAs overexpressed in breast cancers Cold Spring Harbor, NY — The human body produces 100,000 or more different proteins. Yet, amazingly, only two percent of the human genome actually encodes proteins. Nearly 80 percent of the rest of the genome is transcribed into RNA that...
Why calling childhood cancers “rare” is missing the point
September 19, 2016
LabDish blog Childhood cancer is rare, and that categorization can dissuade researchers from studying. But to CSHL’s Chris Vakoc, a cancer researcher who also trained as a medical doctor, the rarity of childhood cancer is not what’s really important. There’s a great tradition in science of studying rare abnormalities in patients, learning something really fundamental, and having it...
To divide or not: a cellular feedback loop that enables new cells to make a fateful decision
July 21, 2016
New research from the Stillman lab has revealed that key components of the DNA replication machinery participate in a feedback loop to control cell proliferation. The proteins—which are often mutated in cancer—provide a direct link between replication and proliferation.
Academic-industry collaboration generates elegant way of pinpointing how a new drug exerts beneficial effects
July 5, 2016
Tested on a newly discovered target and candidate drug for leukemia, the method has broader application Cold Spring Harbor, NY — A collaborative effort by cancer researchers at Cold Spring Harbor Laboratory (CSHL) and chemists at Boehringer Ingelheim (BI), a pharmaceutical firm, has resulted in the identification of a new drug target in leukemia and...
One experiment: How the breast “remembers” a first pregnancy
July 2, 2016
Women consistently report that nursing is easier after a first pregnancy. Some remarkable genomic work led by Professor Greg Hannon provides a biological reason for this effect and shows more broadly how bodily experiences can prepare us to respond to future stimuli. The razor-thin slice of breast tissue pictured here is sampled from a mouse...
Unusual drug target and drug generate exciting preclinical results in mouse models of metastatic breast cancer
December 22, 2015
Cold Spring Harbor, NY – A doctor treating a patient with a potentially fatal metastatic breast tumor would be very pleased to find, after administering a round of treatment, that the primary tumor had undergone a change in character—from aggressive to static, and no longer shedding cells that can colonize distant organs of the body....
New method prevents cells from prematurely halting protein production in certain genetic illnesses
December 14, 2015
Cold Spring Harbor, NY — Improperly formed proteins can cause a host of serious illnesses, from muscular dystrophy to cystic fibrosis. A question of enormous import in research, beyond the challenge of determining how malformed proteins contribute to specific disease processes, is figuring out ways to prevent or reduce the pathologies they cause. Today, a...
Unassuming “Swiss Army knife”-like protein proves lynchpin in a new cancer drug’s therapeutic action
November 30, 2015
Adaptor protein NSD3-short helps researchers explain anti-leukemia drug’s powerful effects Cold Spring Harbor, NY — When preliminary tests show that a new drug has remarkable effectiveness against a lethal illness, everyone wants to know how it works. Often, a mechanism of action is hard to pin down, but when it can be, a candidate drug’s...
Breast cancer survivors show Camila dos Santos what’s important about her research
November 17, 2015
LabDish blog Biology has always felt personal to Assistant Professor Camila dos Santos. Looking back on high school biology in her native Brazil, she remembers, “it was just so interesting to me that there was a field of research that makes you understand how your body works.” Gaining a deeper understanding of how the body...
Rhabdomyosarcoma (RMS) research bolstered by $50,000 gift from Friends of TJ
October 20, 2015
Cold Spring Harbor, N.Y. — On October 14th, The Friends of TJ Foundation presented a check for $50,000 to CSHL Associate Professor Chris Vakoc. Dr. Vakoc is heading the RMS research initiative at Cold Spring Harbor Laboratory. The Friends of TJ Foundation is one of a group of local funders dedicated to find better treatments...
Research connects specific variations in RNA splicing with breast cancer causation
October 1, 2015
SRSF1, a splicing factor, is a known oncogene and is overexpressed in many cancers. The Krainer lab has identified hundreds of splicing events that are regulated by SRSF1 and pinpointed at least one of the critical targets that helps to drive breast cancer.
Scientists discover how a promising anti-leukemia drug harms cancer cells
May 14, 2015
Brd4 is a validated drug target for AML with an inhibitor in clinical trials, yet its precise function has remained unclear. In this study, the Vakoc lab defined how the protein cooperates with hematopoietic transcription factors to create a chromatin signaling cascade that offers additional potential drug targets.
Using CRISPR, biologists find a way to comprehensively identify anti-cancer drug targets
May 11, 2015
The Vakoc lab collaborated with Justin Kinney to develop a new screening method using CRISPR-Cas9 technology. The method targets protein domains, rather than the traditional 5’ exon of the gene, to reveal cancer dependencies and identify new drug targets.
Scientists show the mammary gland ‘remembers’ prior pregnancy, spurring milk production
May 7, 2015
Camila dos Santos, as a postdoctoral researcher in the Hannon lab, identified the epigenetic changes that occur after pregnancy in the mouse mammary gland. The work offers insight into how pregnancy early in life may protect against breast cancer later.
Cancer researcher Dr. Chris Vakoc to receive AACR’s Outstanding Achievement Award
April 17, 2015
Philadelphia, PA and Cold Spring Harbor, NY — The American Association for Cancer Research (AACR) will honor CSHL Assistant Professor Christopher R. Vakoc, M.D., Ph.D., with the 35th annual AACR Outstanding Achievement in Cancer Research Award. The award will be given at the AACR Annual Meeting 2015, which convenes in Philadelphia on Saturday, April 18th....
Twin copies of a gene pair up in embryonic stem cells at a critical moment in their differentiation
March 5, 2015
Team finds that both copies of the Oct4 gene physically come together just as embryonic stem cells begin to develop into tissue-specific cell types Cold Spring Harbor, NY — Imagine a pair of twins that everyone believed to be estranged, who turn out to be closer than anyone knew. A genetic version of this heartwarming...
In a role reversal, RNAs proofread themselves
January 29, 2015
Molecular photographs of an enzyme bound to RNA reveal a new, inherent quality control mechanism Cold Spring Harbor, NY — Building a protein is a lot like a game of telephone: information is passed along from one messenger to another, creating the potential for errors every step of the way. There are separate, specialized enzymatic...
Christina Renna Foundation Raises $30,000 for pediatric cancer research at CSHL
January 26, 2015
Funds will be used to support Sarcoma Research Project The Christina Renna Foundation presented $30,000 to Cold Spring Harbor Laboratory (CSHL) at their 8th annual Angel’s Wish Gala held on January 16, 2015. These funds will be used to support a new Sarcoma Research Project that will look into a rare and often fatal cancer, Rhabdomosarcoma...
One experiment: Sometimes our cells express only one gene copy. Why?
June 1, 2014
Humans, like most mammals, are made up of diploid cells. In the nucleus of each cell there are two copies of every gene, one inherited from each parent. Here, we see the nuclei (circled in white) of several diploid cells from a mouse: neural cells in an early stage of development. Each nucleus contains one...
Among the changes that occur during pregnancy, those affecting the breasts have been found to subsequently modify breast cancer risk. My laboratory investigates how the signals present during pregnancy permanently alter the way gene expression is controlled and how these changes affect normal and malignant mammary development.
Only a small portion of the RNAs encoded in any genome are used to make proteins. My lab investigates what these noncoding RNAs (ncRNAs) do within and outside of cells, where regulators of their expression are located in the genome, and how perturbations of ncRNAs and their regulators contribute to disease.
To ensure that cells function normally, tens of thousands of genes must be turned on or off together. To do this, regulatory molecules - transcription factors and non-coding RNAs – simultaneously control hundreds of genes. My group studies how the resulting gene networks function and how they can be compromised in human disease.
Our cells depend on thousands of proteins and nucleic acids that function as tiny machines: molecules that build, fold, cut, destroy, and transport all of the molecules essential for life. My group is discovering how these molecular machines work, looking at interactions between individual atoms to understand how they activate gene expression, DNA replication, and small RNA biology.
From regulating gene expression to fighting off pathogens, biology uses DNA sequence information in many different ways. My research combines theory, computation, and experiment in an effort to better understand the quantitative relationships between DNA sequence and biological function. Much of my work is devoted to developing new methods in statistics and machine learning.
Our DNA carries the instructions to manufacture all the molecules needed by a cell. After each gene is copied from DNA into RNA, the RNA message is "spliced" - an editing process involving precise cutting and pasting. I am interested in how splicing normally works, how it is altered in genetic diseases and cancer, and how we can correct these defects for therapy.
Chromosomes are covered with chemical modifications that help control gene expression. I study this secondary genetic code - the epigenome - and how it is guided by small mobile RNAs in plants and fission yeast. Our discoveries impact plant breeding and human health, and we use this and other genomic information to improve aquatic plants as a source of bioenergy.
The immense amount of DNA, RNA and proteins that contribute to our genetic programs are precisely organized inside the cell¹s nucleus. My group studies how nuclear organization impacts gene regulation, and how misregulation of non-coding RNAs contributes to human diseases such as cancer.
Despite the development of preventive vaccines, human papillomaviruses (HPVs) still infect more than five million women each year, significantly increasing their risk of cervical cancer. I am working to identify how HPV multiplies so that we may develop drugs that can defeat the virus once it has infected an individual.
Every time a cell divides, it must accurately copy its DNA. With 3 billion “letters” in the human genome, this is no small task. My studies reveal the many steps and molecular actors involved, as well as how errors in DNA replication are involved in diseases that range from cancer to rare genetic disorders.
Cancer cells achieve their pathogenicity by changing which genes are on and off. To maintain these changes in gene expression, cancer cells rely on proteins that interact with DNA or modify chromatin. My group investigates how such factors sustain the aberrant capabilities of cancer cells, thereby identifying new therapeutic targets.
The research of my lab focuses on normal and malignant hematopoietic stem and progenitor cells, specifically early erythroid progenitors and leukemic cells. We utilize both CRISPR/Cas functional genomic and forward chemical genomic approaches to uncover critical genes and small chemical compounds regulating the self-renewal of normal and malignant hematopoietic stem and progenitor cells. The ultimate goal of our research is to identify novel therapeutics for treatment-resistant hematopoietic malignancies including myelodysplastic syndrome and acute leukemia through targeting of novel self-renewal pathways and metabolic vulnerabilities.