Amanda Taylor Receives 5 Year NCI Fellowship

Amanda Taylor

Amanda Taylor

Amanda Taylor, a doctoral candidate in the Genetics, Genomics and Cancer Biology Program conducting her thesis research in the laboratory of Dr. Steven McMahon has received a 5 year fellowship from the National Cancer Institute/NIH totaling $221,400. The award was made for a project entitled: “Myc overexpression regulates metabolic reprogramming by mitochondrial polymerase”.




Dr. Curry Receives Grant to Investigate Head and Neck Cancer

Joseph Curry, MD

Joseph Curry, MD

Joseph Curry, MD, Assistant Professor in the Department of Otolaryngology – Head and Neck Surgery, has been selected to receive this year’s American Head and Neck Society/American Academy of Otolaryngology-Head and Neck Surgery Foundation Young Investigators Combined Grant. Under the mentorship of Dr. Ubaldo Martinez-Outschoorn, Assistant Professor of Medical Oncology and Dr. William Keane, Chairman of the Department of Otolaryngology – Head and Neck Surgery, Dr. Curry will investigate metabolic coupling between cancer and stromal cells in head and neck cancer and its role in carcinoma cell proliferation and resistance to apoptosis.

The American Academy of Otolaryngology-Head and Neck Surgery Centralized Otolaryngology Research Efforts (CORE) grants program is a collaboration of several societies, foundations, and industry supporters focused on providing support for research in the field of otolaryngology-head and neck surgery.




Dr. Gabriele Di Sante Awarded American Italian Cancer Foundation Research Fellowship

Dr. Gabriele Di Sante

Dr. Gabriele Di Sante

Gabriele Di Sante, PhD, a post-doctoral fellow in Dr. Pestell’s lab, has been awarded a 2014-2015 Fellowship from the American Italian Cancer Foundation. For more details about the American Italian Cancer Foundation, please see their website.



Dr. Pestell and Austrailian Prime Minister

Dr. Richard Pestell and the Honorable Tony Abbott

Dr. Richard Pestell and the Honorable Tony Abbott

On June 10th 2014 Dr. Pestell attended an engagement in New York with the Prime Minister of Australia, the Honorable Tony Abbott, accompanied by several cabinet members. Dr. Pestell discussed with these individuals some new initiatives at Jefferson along with the “Leg Up not a Handout” initiative. In the picture you can see Dr. Pestell going over that plan with Prime Minister Abbott to strengthen our international relations here at the Kimmel Cancer Center at Thomas Jefferson University.



KCC Collaborating with BioBank Graz

From left to right Prof. Berthold Huppertz, Dr. Richard Pestell, Prof Peter Holzer and Amir Oryan.

From left to right Prof. Berthold Huppertz, Dr. Richard Pestell, Prof Peter Holzer and Amir Oryan.

Dr. Pestell meets with representatives from Medical University Graz and BioBank Graz as they discuss the growing MOU partnership agreement between Medical University Graz and the Kimmel Cancer Center at Thomas Jefferson University.



Holistic Care at the KCC

Dr. Richard Pestell and Dr. Pratap are featured at this classical yoga event entitled “Rethinking Cancer” on May 18th in the Hamilton building. The event was held to create awareness and the presence of mindfulness stress reduction within cancer patients.



KCC Post-doctoral selected as AICF Fellow

Dr. Claudia Capparelli

Dr. Claudia Capparelli

Claudia Capparelli, a post-doctoral fellow in  Dr. Andrew Aplin’s lab, has been selected as an American-Italian Cancer Foundation (AICF) Fellow for the 2014-15 academic year!   Ten were chosen out of an extraordinary pool of Italian talent and she will join several other accomplished second-year AICF fellows who are currently pursuing careers in cancer research in the US.

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Is Good Health a Choice?: Richard Pestell at TEDxOccidentalCollege

In this talk, given at the TEDxOccidentaCollege meeting, Dr. Pestell explores cultural assumptions that drive cancer seeking behavior. He will reveal solutions that will empower you to live healthier starting today.



Dr. Aplin Wins Innovation Award

Dr. Andrew Aplin

Dr. Andrew Aplin

Congratulations to Dr Andrew Aplin, Department of Cancer Biology, has received the 2014 Jefferson Medical College Michael and Melina Pellini Award for Innovation in the Biomedical Sciences. The award is given “For the elucidation/description of a specific discovery, technique, or instrument/device that has led to new concepts or approaches to experimentation or patient care.”




Dr. Richard Pestell Receives Advance Global Australian Award in Biotechnology Category

Former Australian Prime Minister John Howard and Dr, Richard Pestell

Former Australian Prime Minister John Howard and Dr, Richard Pestell

Dr. Pestell received the award for his work at the Kimmel Cancer Center at Jefferson as well as Prostagene, LLC, which is a biotechnology company he founded. Please see this Financial Review Article for more information bout this year’s Advance Global Australian Awards. Also please see this video clip of Dr. Pestell receiving the Advance Global Australian Award in Biotechnology at the Sydney Opera House.



Dr. Gomella elected to the Clinical Society of Genitourinary Surgeons

Dr. Leonard Gomella

Dr. Leonard Gomella

Leonard G. Gomella, MD, The Bernard W. Godwin Professor of Prostate Cancer, Chairman, Department of Urology, Associate Director, Jefferson Kimmel Cancer Center, Clinical Director Jefferson Kimmel Cancer Center Network, Editor-in-Chief, Canadian Journal of Urology has been elected to the Clinical Society of Genitourinary Surgeons. This is considered one of the most prestigious societies in the field with active membership limited to 25 of the top academic urologists in the US.



Jefferon’s Kimmel Cancer Center Holds 5th Annual Men’s Event

Jefferson’s Kimmel Cancer Center hosted its 5th Annual Men’s Event to benefit prostate cancer research and awareness at the Prime Rib Restaurant on November 14.

Below are some photos of the night, award ceremony and entertainment provided by Comedy Central’s “100 Greatest Stand-Ups of All Time,” Jim Breuer of Saturday Night Live.


“Spirit of Caring” Awardee:

Wm. Kevin Kelly, D.O.

Professor, Medical Oncology and Urology,
Director, Division of Solid Tumor Oncology

The “Spirit of Caring Award” is presented to an individual to recognize outstanding leadership in cancer research and the hope they hold for improving the quality of life in every community.

“Spirit of Courage” Awardee:
Anthony DiPrimio, PhD

Author, Prostate Cancer: What Men Need to Know About this Disease and Its Treatment

The “Spirit of Courage Award” is presented to an individual who has demonstrated great personal courage, strength and dignity while battling cancer and supporting others in their fight against cancer.

“Spirit of Commitment” Awardee:
Neal Rodin

President, International Financial Company, LLC

The “Spirit of Commitment Award” is presented to an individual to recognize outstanding commitment to supporting the work of the Kimmel Cancer Center through personal and professional contributions dedicated to finding a cure.

“Spirit of Innovation” Awardee:
Dendreon:
The company applies its expertise in antigen identification, engineering and cell processing to produce active cellular immunotherapy (ACI) product candidates designed to stimulate an immune response. They pioneered a novel, first in class autologous immunotherapy first approved for the treatment of advanced prostate cancer. Dendreon is headquartered in Seattle with corporate operations based locally in the Delaware Valley and manufacturing plants in Georgia and California.

The “Spirit of Innovation” Award is presented to an organization whose innovation in cancer measurably improves business and/or clinical processes that impact product development, prevention programs, research, or patient care.



ACS-IRG Pilot Projects Awarded for 2013

Left to Right: Dr. Jordan Winter, Dr. Lara Weinstein, Dr. Aejaz Sayeed, Dr. Richard Pestell, Dr. Tali Gidalevitz, Larry Slagle, Ruth Ann Dailey, Dr. Marja Nevalainen

The Jefferson Kimmel Cancer Center hosted the Annual ACS-IRG Luncheon on September 17th to announce the 2013 Pilot Project award recipients from Thomas Jefferson University. Awardees include Sheikh Aejaz Sayeed, PhD from the Department of Cancer Biology; Jordan Winter, MD, from the Department of Surgery; Yaron Moshel, MD, PhD from the Department of Neurological Surgery; Tiffany Avery, MD, MPH from the Department of Medical Oncology; Lara Carson Weinstein, MD, MPH from the Department of Family & Community Medicine and from Drexel University,  Tali Gidalevitz, PhD from the Department of Biology. Each Awardee briefly explained their research projects to Ruth Ann Dailey, Vice President, Corporate and Distinguished Partners and Larry Slagle, Distinguished Giving Director, of the East Central Division of the American Cancer Society. Ms. Dailey and Mr. Slagle explained the ACS mission and offered ways in which the Pilot Project recipients would be able to assist them in that mission.



Kimmel Cancer Center “All Hands Meeting”

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on September 11, 2013. Dr. Richard Pestell, Director of the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address. Awards were presented in several categories. Two “Special Recognition” awards where presented to  Andrew Quong, PhD and Jeanine Voll (not pictured). The “Discovery of the Year” Awards was presented to Alexander Mazo, PhD. The Nursing Award was presented to Tamara McGovern, RN. The Basic Science Award was awarded to Dr. Andrew Aplin (not pictured). A Special Team Nursing Award was presented to  the ONCare Nursing team. A Special Administration Award was present to the ONCare Administrative Team.

Dr. Alexander Mazo Receives "Discovery of the Year" Award from Dr. Richard Pestell

Dr. Alexander Mazo Receives "Discovery of the Year" Award from Dr. Richard Pestell

Dr. Andrew Quong Receives "Special Recognition" Award from Dr. Richard Pestell

Dr. Andrew Quong Receives "Special Recognition" Award from Dr. Richard Pestell



ONCare Administrative Team Receives Special team Admimistration Award From Dr. Neal Flomenberg

ONCare Administrative Team Receives Special team Admimistration Award From Dr. Neal Flomenberg



ONCare Nursing Team Receives Special Team Nursing Award From Dr. Neal Flomenberg

ONCare Nursing Team Receives Special Team Nursing Award From Dr. Neal Flomenberg


Ms. Tamara McGovern Receives Nursing Award from Dr. Neal Flomenberg

Ms. Tamara McGovern Receives Nursing Award from Dr. Neal Flomenberg





A Link between Hormones and DNA Repair Provide New Clues to Treat Advanced Prostate Cancer

Karen Knudsen, Ph.D.

For advanced prostate cancers, new strategies for therapeutic intervention are urgently needed, and require a better understanding of how tumor cells go from slow growth to aggressive behaviors that threaten patient lives.

A new study, published by Thomas Jefferson University’s Kimmel Cancer Center researchers in the September 11th online edition of the journal Cancer Discovery, showed that hormones promote DNA repair, and that this process is critical for prostate tumor cell survival. The research also revealed a new therapeutic target that has potential for improving management for patients with advanced disease.

“We’ve known for decades that in prostate cancer, disease development and progression are dependent on the action of androgens (testosterone), but the means by which androgens promote these events remain poorly defined,” says lead author Karen Knudsen Ph.D., Professor of Cancer Biology at Thomas Jefferson University and the Deputy Director for Basic Science at Jefferson’s Kimmel Cancer Center. “The concept that androgens assist cancer cells in repairing DNA damage helps to explain how tumors evade therapeutic intervention. The good news is that these discoveries may point toward a new way to treat patients with aggressive disease.”

Inhibiting androgens is the first line of treatment for advanced prostate cancers, but this therapeutic strategy is only transiently effective, generally because tumors develop “rescue” pathways to restore androgen action. To try and understand the implications of this process, and to find means for treating such advanced disease, the researchers identified new molecular pathways involved in relaying messages from the androgen receptor to DNA repair genes. They found that androgens enhanced DNA repair by turning on the gene for a powerful DNA repair enzyme called DNAPK.

When the researchers inhibited DNAPK, they saw a reduction in tumor cell growth, and using disease models, observed that standard therapies were more effective. By acting on a more selective target in the androgen pathway, the researchers hope to improve androgen inhibition strategies and to help patients who no longer respond to androgen-inhibition-based therapies.

“These findings give us new insight into how tumors can evade existing therapies. Most importantly, the fact that prostate cancer cells use androgens and DNAPK to survive therapeutic intervention unveiled an Achilles heel for advanced tumors that we can capitalize on,” said Dr. Knudsen.

The researchers discovered that pharmacologic agents, some of which are already in clinical trials for other malignancies, can be used to suppress DNAPK activity. “The next step for us is to translate these findings into the clinical setting. Luckily, our prostate group is highly collaborative, and we are already in the midst of designing clinical trials to fast-track DNAPK inhibitors into the clinic”, said Dr. Knudsen. “There are always challenges in introducing new therapeutic targets, but if we are correct, there is every reason to believe that DNAPK inhibitors can be used to improve outcomes for patients with advanced disease.”

The study from Dr. Knudsen’s laboratory was a result of an inter-institutional team effort, including contributions of the first author and graduate student Jonathan F. Goodwin, key collaborators from the Thomas Jefferson University Department of Radiation Oncology, Dr. Adam P. Dicker, and Dr. Robert B. Den, and from the University of Michigan, Dr. Felix Y. Feng.

The authors declare that they have no conflicts of interest.

Media Only Contact:
Edyta Zielinska
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 9/11/2013



KCC Researchers Awarded $480,000 from Breast Cancer Research Foundation

Richard Pestell, MD, PhD and Andrew Quong, PhD

The Breast Cancer Research Foundation recently announced that Dr. Richard Pestell and Dr. Andrew Quong received unanimous approval for studies in breast cancer, the second most prevalent cancer-related cause of death in women in the United States.

Beginning October 1, 2013, Dr. Pestell will receive $240,000 to continue the “Molecular Genetic determinants of Breast Cancer Stem Cells” study and Dr. Quong will receive $240,000 to continue the “Clinical Proteomics for Breast Cancer Diagnostics” study.

Dr. Pestell’s study will focus on basal breast cancer including triple negative breast cancer, defined by the absence of three receptors (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 [HER2]). Triple negative breast cancer is prominent among African-American women, and currently no targeted therapies for this type of breast cancer exist. Within human breast cancer a subset of cells have characteristics of stem cells (BTIC), which may contribute to recurrence and therapeutic resistance. The mechanism by which the gene DACH1 inhibits BTIC is being determined as a new approach to enhance therapeutic responsiveness. Dr. Pestell’s findings over the last year that DACH1 binds to and enhances function of the p53 tumor suppressor, but fails to bind mutations of p53 identified in human breast cancer, adds further weight to the original hypothesis that DACH1 is a breast tumor suppressor. Dr. Pestell’s studies in 2012-2013 will continue to define the role of endogenous DACH1 as a breast cancer suppressor.

Support from BCRF has also allowed Dr. Quong to complete his studies examining changes in protein levels in breast tumors. From these observed changes, Dr. Quong’s team found changes in the metabolism of tumor cells that are related to the local microenvironment of the tumor. These changes in metabolism can potentially be exploited for both imaging and drug development. In addition, Dr. Quong has continued his work identifying markers that are indicators of toxicity and response to therapy.

In 2012-2013, the goal of Dr. Quong’s research is to determine new strategies for patient treatment that include radiation therapy. By measuring the protein and gene expression in tumors, his will use this information for choosing treatment and also monitoring the patients’ response to treatment both for effectiveness and adverse side effects.



Researchers Find New Clues to Treat Rare and Aggressive Inflammatory Breast Cancer

Massimo Cristofanilli, M.D.

A study led by investigators from Thomas Jefferson University’s Kimmel Cancer Center has discovered molecular clues that may help physicians therapeutically target inflammatory breast cancer (IBC), a highly aggressive form of breast cancer.

Their study, reported in the June 21 online issue of Breast Cancer Research and Treatment, identified two molecules (ALK and FAK1) involved in the IBC cancer pathway. Drugs already exist that inhibit both of these two cancer-promoting proteins at the same time, which the researchers are now testing in animal preclinical studies.

“Women diagnosed with inflammatory breast cancer are in great need of therapies that are tailored to this aggressive form of breast cancer. Survival rates are much lower than for other forms of breast cancer,” says the study’s lead author Sandra V. Fernandez, Ph.D., Assistant Professor in the Medical Oncology department at Jefferson.

IBC is a particularly aggressive and highly metastatic form of breast cancer characterized by very rapid onset of progression— weeks to a few months — and metastasis that spreads quickly to the brain, bones, and soft tissues. The three-year survival rate is 40 percent for IBC patients compared with 85 percent in other forms of breast cancer. Additionally, IBC patients are younger when diagnosed.

The disease is also difficult to diagnose because it appears as redness and swelling of the breast. There are no classic tumor masses.

“Because of how this cancer looks, physicians often think it is dermatitis, or inflammation, or an infection, such as mastitis. I know of many patients who were misdiagnosed from the start, and by the time they were referred to an oncologist, their cancer had progressed,” says the study’s senior investigator, Massimo Cristofanilli, MD, FACP, Professor of Medical Oncology and Director of the Jefferson Breast Care Center.

“We need to improve both diagnosis and treatment of this cancer, which is on the rise for reasons that are not understood,” he says.

The advances reported in the study were possible because the research team developed a new animal model of IBC, derived from tumor  cells from a patient with metastatic triple negative (estrogen receptor-negative, progesterone receptor-negative, Her2-negative) inflammatory breast cancer under an IRB-approved study. At the present, there are few animal models to study this particular disease.

In addition to identifying some of the pathways involved in IBC, the researchers were able to characterize the pattern of spread of the disease, which moved quickly to organs and the brain. They found that clumps of the cancer — not tumor masses — obstruct lymphatic channels in the breast, causing the swelling of breast tissues.

“This animal model is a really important tool to use to study IBC progression and metastasis, and to test potentially beneficial drugs,” says Dr. Fernandez.

Researchers from the University of Texas M D Anderson Cancer Center and Fox Chase Cancer Center contributed to the research.

The study was supported by the American Airlines-Komen for the Cure Foundation Promise Grant KGO81287, NIH NCI 1R01 CA 138239, and the Inflammatory Breast Cancer Foundation.

The authors declare that they have no conflicts of interest.

For more information, contact Jackie Kozloski, 215-955-5296, jackie.kozloski@jefferson.edu.



Protein in Blood Exerts Natural Anti-Cancer Protection

Renato V. Iozzo, M.D.

Researchers from Thomas Jefferson University’s Kimmel Cancer Center have discovered that decorin, a naturally occurring protein that circulates in the blood, acts as a potent inhibitor of tumor growth modulating the tumor microenvironment.

The study, published June 24 online in the Proceedings of the National Academy of Sciences (http://www.pnas.org/content/early/2013/06/19/1305732110.abstract), suggests it may be possible to harness the power of this naturally occurring anticancer agent as a way to treat cancer, including metastases.

In several different publications it has been described the ability of decorin to affect a number of biological processes including inflammatory responses, wound healing, and angiogenesis.

In this new article, the study’s senior investigator, Renato Iozzo, M.D., Ph.D., has labeled decorin a “soluble tumor repressor” — the first to be found that specifically targets new blood vessels, which are pushed to grow by the cancer, and forces the vessel cells to “eat” their internal components. This reduces their potential to feed the cancer overall causing an inhibition of tumor progression.

“The tumor suppressors we all know are genes inside tumors that a cancer deletes or silences in order to continue growing. I call decorin a tumor repressor because its anti-tumor activity comes from the body, outside the cancer,” says Dr. Iozzo, Professor of Pathology & Cell Biology, Biochemistry & Molecular Biology at Kimmel Cancer Center.

“Decorin is a soluble compound that we found has a powerful, natural protective effect against cancer — an exciting finding that we believe will open up a new avenue for both basic research and clinical application,” Dr. Iozzo says. “Acting from the outside of the cells, decorin is able to modify the behavior of the cancer cells and of the normal cells in order to slow down the progression of the tumor. For this reason, decorin acts as a guardian of the matrix, the complicated structure built around the cells in our body.”

Absence of decorin promotes tumor growth

Decorin has long been known to be involved in human development. It is so named because deposits of decorin “decorate” collagen fibrils after the human body forms.

A second pool of decorin has been found circulating in blood after production by connective tissue throughout the body. This connective tissue is part of the extracellular matrix, which provides both structural support and biological regulation of tissue cells.

But no one has understood the biological function of this second pool of decorin, according to Dr. Iozzo.
The research team, including the two co-first authors, Simone Buraschi, Ph.D., and Thomas Neill, a graduate student, who work in the laboratory of Dr. Iozzo, decoded the function of soluble decorin. They found that addition of exogenous decorin to the tumor microenvironment induces autophagy, a mechanism by which cells discard unnecessary or damaged intracellular structures. “This process regulates a lot of cellular activities,” says Dr. Iozzo.

The researchers specifically found that decorin evoked autophagy in both microvascular and macrovascular endothelial cells — cells that line the interior surface of blood vessels.

“This matters because autophagy can exert a potential oncosupressive function by acting to discard critical cell components that would otherwise be involved in promotion of tumor growth through angiogenesis, the production of new blood vessels that can provide nutrition to the tumor,” Dr. Iozzo says. “In contrast, absence of decorin permits tumor growth.”

Therefore, the presence of decorin in the surroundings of the tumor is essential to control tumorigenesis and formation of new blood vessels, he says. Moreover, Dr. Iozzo’s laboratory has characterized for the first time Peg3, a known tumor-suppressor gene, as a master player in the autophagy process induced by decorin. “This discovery is important as it opens up to the study of new unexplored genes and signaling pathways in the field of autophagy,” he says.

“Circulating decorin represents a fundamental cellular process that acts to combat tumor angiogenesis,” Dr. Iozzo says. “Treatment based on systemic delivery of decorin may represent a genuine advance in our ongoing war against cancer.”

The study was funded by the National Institutes of Health grants R01 CA39481, R01 CA47282, and R01 CA120975.

Collaborating researchers from LifeCell Corporation, in Branchburg, New Jersey, and Goethe University in Frankfurt, Germany, also contributed to the study.

For more information, contact Jackie Kozloski, 215-955-5296, jackie.kozloski@jefferson.edu.



Researchers Discover Molecule That Drives Aggressive Breast Cancer

Richard G. Pestell, M.D., Ph.D.

Recent studies by researchers at Thomas Jefferson University’s Kimmel Cancer Center have shown a gene known to coordinate initial development of the eye (EYA1) is a powerful breast tumor promoter in mice. The gene EYA1 was also shown to be overexpressed in a genetic breast cancer subtype called luminal B.

The scientists found that excess activity of this gene —EYA1 — also enhances development of breast cancer stem cells that promote resistance to cancer therapy, recurrence, and poor survival.

Because EYA1 is an enzyme, the scientists are now working to identify a natural compound that could shut down EYA1 activity, says Richard Pestell, M.D., Ph.D., Director of Kimmel Cancer Center.

“It was known that EYA1 is over-expressed in some breast cancers, but no one knew what that meant,” he says. “Our studies have shown the enzyme drives luminal B breast tumor growth in animals and the enzyme activity is required for tumor growth.”

In a mouse model of aggressive breast cancer, the research team targeted a single amino acid on the EYA1 phosphatase activity. They found that inactivating the phosphatase activity of EYA1 stopped aggressive human tumors from growing.

“We are excited about the potential of drug treatment, because it is much easier to develop a drug that targets a phosphatase enzyme like EYA1, than it is to target a gene directly,” he says.

Tracing how EYA1 leads to poor outcomes

The study, which was published in the May 1 issue of Cancer Research, examined 2,154 breast cancer samples for the presence of EYA1. The researchers then linked those findings to patient outcomes. They found a direct relationship between increased level of EYA1 and cyclin D1 to poor survival.

They then chose one form of breast cancer —luminal B — and traced the bimolecular pathway of how EYA1 with cyclin D1 increases cancer aggressiveness. Luminal B breast cancer, one of five different breast cancer subtypes, is a hormone receptor-positive form that accounts for about 20 percent of human breast cancer. It is more aggressive than luminal A tumors, a hormone receptor-positive cancer that is the most common form of breast cancer.

Their work delineated a string of genes and proteins that are affected by EYA1, and they also discovered that EYA1 pushes an increase in formation of mammospheres, which are a measure of breast cancer stem cells.

“Within every breast cancer are breast cancer stem cells, which give rise to anti-cancer therapy resistance, recurrence and metastases,” Dr. Pestell says. “We demonstrated in laboratory experiments that EYA1 expression increase the number of mammospheres and other markers of breast cancer stem cells.”

“As the EYA1 phosphatase activity drove breast cancer stem cell expansion, this activity may contribute to worse survival,” he says.

This study was supported in part by the NIH grants RO1CA132115, R01CA70896, R01CA75503, R01CA86072 and P30CA56036 (RGP), a grant from the Breast Cancer Research Foundation (RGP), a grant for Dr. Ralph and Marian C. Falk Medical Research Trust (RGP), Margaret Q. Landenberger Research Foundation, the Department of Defense Concept Award W81XWH-11-1-0303.

Study co-authors are, from Kimmel Cancer Center: first author Kongming Wu, Zhaoming Li, Shaoxin Cai, Lifeng Tian, Ke Chen, Jing Wang and Adam Ertel; Junbo Hu, from Huazhong University of Science and Technology, China; and Ye Sun, and Xue Li from Boston Children’s Hospital.

For more information: Jackie Kozloski, 215-955-5296, jackie.kozloski@jefferson.edu.



Need to Analyze Your Next-Generation Sequencing Data? Thomas Jefferson University’s New Web-Based Resource Makes the Task Easy

Isidore Rigoutsos, Ph.D.

In the early 1990s, an international effort was launched by the U.S. Department of Energy and the National Institutes of Health to sequence the human genome. The project took 13 years, involved many scientists in several countries, and cost $2.7 billion (in FY 1991) dollars.

Since then, technological advances and the advent of next generation sequencing have greatly increased the speed at which the genome or the transcriptome of a model organism such as human or mouse can be sequenced. Nowadays, a typical sequencing platform can generateseveral billion bases of DNA or RNA in the course of a few days and can do so at a far lower cost.

However, such an embarrassment of riches poses difficulties for the typical research groups who would like to make use of this technology but are neither accustomed nor equipped to handle the great amounts of data that can now be generated. To help address this problem, Thomas Jefferson University is making available to researchers and clinicians such an analytical capability on the web.

The resource, referred to as HandsFree, is a system that was designed and implemented by the Computational Medicine Center at Thomas Jefferson University. The goal of HandsFree is to provide researchers and clinicians at Thomas Jefferson University and Hospitals with the ability to analyze the large datasets that next generation sequencing platforms generate. And since HandsFree is web-based, scientists at other universities, in the Delaware Valley and elsewhere, could also take advantage of it.

“It is a unique resource to academic research and medicine,” says Isidore Rigoutsos, Ph.D., Director of the Center. “I don’t know of any other research institution or medical center that currently makes a similar system available to their researchers and clinicians.”

How does it work? Dr. Rigoutsos offers as an example a researcher who wants to understand a particular aspect of the biology of Alzheimer’s disease, and who has brain samples taken from a deceased patient, as well as samples from a normal brain. The investigator would give the samples to the sequencing facility at the Kimmel Cancer Center at Jefferson and several days later she will get back data files typically containing 200 million sequences for each sequenced sample, he says.

“This is where HandsFree comes in,” Dr. Rigoutsos says. “The investigator can access HandsFree through her computer browser, securely transfer the sequencing dataset to the HandsFree web-server, and answer a few questions about the type of data and desired analyses. At this point, the data will be placed in a queue with other datasets for analysis by the Computational Medicine Center’s computers. When the dataset reaches the front of the queue, it will be quality-trimmed and preprocessed, then mapped on the corresponding genome followed by a series of analyses that are typical for such data.”

“The system will also generate genomic maps for the investigator to also enable subsequent off-line visual exploration. The generated results and maps are then placed back on the HandsFree web-server and the investigator is notified through email that the output is ready for collection,” he says.

“The whole process is as hands-free as it can get for these kinds of datasets,” Dr. Rigoutsos says. “The investigator still has some work ahead of them but the system does all the ‘heavy lifting’ for them taking the guess-work out and making this kind of analysis easy to harness.”

It took his team one and a half years to put the HandsFree system together. The underlying pipeline uses both publicly available standard tools as well as tools that the team specifically developed to automate the whole process. “HandsFree enables others to access the very same pipeline that we use ourselves for our own basic research. In this regard, the pipeline’s components have already been ‘vetted’ by us,” says Dr. Rigoutsos.

Very importantly, the system handles the data in a secure fashion, he adds. “Any data that the investigator exchanges with HandsFree is encrypted in both directions. Moreover, the processing and analyses of the data are carried out by the Center’s machines in a separate and secure high performance computing facility.”

Currently, the HandsFree system can accommodate DNA and RNA datasets generated by several popular sequencing platforms, from both human and mouse. “For these datasets, the user can carry out a number of standard analyses at the click of a button,” Dr. Rigoutsos says. “A whole host of additional capabilities is in the process of being implemented and will be enabled in HandsFree in the months ahead.”

The system is now available to researchers, and the cost for analyzing these datasets “is very reasonable,” he says. “HandsFree will help advance medical science, and we are very pleased to have it online and available to our researchers and to others.”

The system can be accessed at http://cm.jefferson.edu/HandsFree

For more information, contact: Jackie Kozloski, 215-955-5296 or jackie.kozloski@jefferson.edu.