Northwestern Grad Students Contribute to Novel, Networked Physical Sciences Approach to Cancer Research

Northwestern Grad Students Contribute to Novel, Networked Physical Sciences Approach to Cancer Research

Dhwanil Damania

Dhwanil Damania

Two Northwestern graduate students, Dhwanil Damania (Biomedical Engineering) and Yolanda Stypula (Interdepartmental Biological Sciences) are co-authors on an important new paper just published in Scientific Reports. The paper is the outcome of a ground-breaking collaborative effort by a network of 12 National Cancer Institute-funded Physical Sciences-Oncology Centers (PS-OC).

The goal of this effort was to compare the molecular and biophysical attributes of non-tumorigenic (MCF-10A) cells and metastatic breast cancer cells (MDA-MB-231) in culture to determine the nature of physical changes in cell structure and activity associated with metastasis.  PS-OC investigators found dramatic differences in the capacity of the metastatic cells for migration and adhesion compared to non-metastatic cells.  Cell shape, oxygen stress response and protein profiles also differed markedly between these cell types.

Overall, the metastatic cells were found to be more physically flexible and stress-tolerant than the non-tumorigenic cells.  PS-OC investigators were able to model potential linkages between the molecular and physical characteristics of the cell lines using molecular network analysis.

This pilot study, created by a large array of physical and life scientists and clinicians, demonstrates the potential of a large scale team approach, such as the Physical Science-Oncology Centers network, to address the “big questions” of cancer research.

Yolanda Stypula

Yolanda Stypula

Damania, who was recently awarded a doctorate in biomedical engineering and Stypula contributed to this work using a unique imaging technique developed in Professor Vadim Backman’s lab (Biomedical Engineering), called partial wave spectroscopic (PWS) microscopy, to compare the nanoscale architecture of the nuclei of the two different cancer cell types which is otherwise invisible by traditional microscopy/histopathology.  They found that the nuclei of the metastatic cells were significantly more disorganized than those of the non-metastatic cells.    Previous studies by the Backman group have shown that these nuclear alterations are a marker for early stage carcinogenesis in solid tumors.

According to Damania and Stypula “From a logistic perspective, it is exciting and rewarding to see how the final paper came together as an end-result of all the hard work of many researchers, coordinators and PSOC/NCI staff.  We believe that this manuscript would serve as an example for other groups to carry out multi-institutional studies.”

Both Damania and Stypula have been supported by Northwestern PS-OC and have made significant contributions to the work of the Center.  Damania previously won a PSOC Young Investigator Trans-Network award in 2010 for a collaborative project with the Scripps Research Institute.  Their work intercalates with the efforts of the Northwestern PS-OC to determine the fundamental rules governing how DNA is configured, modified and expressed in normal and tumor cells.

Trainees Win Young Investigators’ Trans-network Award

Northwestern University Physical Sciences-Oncology Center (NU PS-OC) trainees Joo Sang Lee, Behnam Nabet, and Eliza Small, along with team member Subhayjyoti De of the Dana Farber Cancer Institute PS-OC, have won a one-year, $15,000 Young Investigators’ Trans-network Award from the National Cancer Institute.

The award supports the team’s innovative project “Identifying the impact of nuclear architecture in the regulation of metabolic pathways,” where they will investigate how genes involved in the regulation of metabolic pathways are spatially distributed in the cell nucleus and how this distribution is altered in cancer cells compared to their normal counterparts. The collaboration brings together both computational biologists and cancer biologists from the two centers.

“This project is a mosaic of orthogonal approaches mastered in three very diverse labs in the two PS-OCs, said Joo Sang Lee, project leader. “It not only brings together computational biologists and experimental cancer biologists, but it also integrates the studies on cancer genomics and epigenetics with those on cancer metabolism.”

The team formulated their proposal over the course of the 4-day Annual PS-OC Network Investigators’ Meeting in April of this year. Selected proposals were submitted by each center for review by the PS-OC Steering Committee, who evaluated proposals on their innovative physical sciences perspective, relevance to major cancer issues, and trans-network collaboration.

Trainees Lee and De will use their computational biology and mathematical modeling expertise to computationally analyze the human metabolic network model and genomic proximity data to identify how the genes encoding enzymes for the metabolic pathways are distributed in the three dimensional genomic packaging. This analysis will allow cancer biologists Nabet and Small to test predictions on the altered proximity of a set of enzyme-coding genes responsible for deregulation of metabolic pathways in cancer.

“I am very excited that the NCI recognized our efforts to bring together computational biologists and cancer biologists within the PS-OCs. By combining these disciplines to work on a common goal, we will model the disease, ask new questions, and then directly test them in the lab,” said Nabet. By identifying the key differences in cancer cells, the team hopes to elucidate the role of chromatin organization in the deregulated metabolism seen in cancer.

Lee and his team are grateful not only for the award, but also of the experience in developing the proposal. “I had the opportunity to sharpen my skills through all the steps of the process, such as organizing a competitive and interdisciplinary team of fellow young investigators, designing a creative and at the same time feasible research project, and writing a clear and strong research proposal,” Lee said. “With this exceptional collaboration, I am confident our team will be able to unveil strategies used by cancer cells to control their metabolism through alterations in their nuclear architecture.”

New Discoveries from NU Physical Sciences-Oncology Center Uncover the “Rules” Governing Gene Transcription

A trio of ground-breaking publications from researchers in Northwestern’s Physical Sciences-Oncology Center (NU-PSOC) has revealed important new methodological advances that have led to a new understanding of the forces governing the regulation of gene expression.   This field is the bedrock for understanding the fundamental aspects of health and disease as it is the “decryption” of the messages carried in our genes that is the important first step in determining which proteins, the major “working” molecules in our cells, are produced in response to changes in the cellular environment.  Regulation of the expression of genes is very tightly controlled in normal cells and aberrant expression is associated with a broad range of diseases, especially cancer.  The length and complexity of DNA requires that it be tightly bundled in cells and the question of how specific genes are accesses by the cell’s decrypting molecules has been a question that has long tantalized researchers.

These new studies produced by the laboratories of Dr. Eran Segal, a collaborator from the Weizmann Institute in Israel, and Drs. Jonathan Widom and Ji-Ping Wang have succeeded in pulling back the curtain on these most fundamental aspects of biology by developing highly sensitive methods to examine how genes are packed in the cell and the factors in terms of location, orientation, and organization of specific genes that affect the conditions under which genes are expressed.   Prof. Segal and colleagues, publishing in a June edition of Nature Biotechnology (volume 30: no. 6, pp. 521-530) has developed a method for high-throughput measurements of carefully designed large-scale promoter (DNA sequences that precede protein-coding regions of genes) libraries that will allow researchers to uncover the ‘regulatory code’ that translates DNA sequence into expression.  His lab has also demonstrated a mechanism for fine-tuning gene expression by changing DNA promoter sequences to disfavor the binding of proteins, known as histones which wrap DNA into inaccessible balls, can increase gene expression (Raveh-Sadka et al. Nature Genetics vol. 44 no. 7:  pp. 743-750, 2012).

This work is complemented by the recent publication in Nature(vol. 486 pp. 497-501, 2012) by Kristin Brogaard, a recent NU PhD working in collaboration with the NU-PSOC Bioinformatics Core, describing a new, highly sensitive method for examining the rules governing how DNA is wound up around histone proteins for compaction into cells.  The profound influence of Prof. Jonathan Widom, founding director of Northwestern’s Physical Science-Oncology Center, on this work is not diminished by his untimely death last July.   He guided the intellectual foundation and methodological approaches that led to these breakthroughs.

Jonathan Licht MD, Johanna Dobe Professor and Chief of the Division of Hematology/ Oncology in the Robert H. Lurie Comprehensive Cancer Center in the Northwestern University Feinberg School of Medicine and the NU-PSOC’s Senior Investigator commented “It is becoming increasingly clear that acquired mutations in the machinery that underlies the way in which DNA is packaged into chromatin are major drivers of the development of tumors in humans.  The work of the PSOC has allowed the elucidation of the normal rules by which chromatin is arranged in the cell.  This will allow us to understand what’s going wrong in cancer and how that might be remedied.”

The Northwestern Physical Sciences-Oncology Center, a collaboration between the Chemistry of Life Processes Institute and the Robert H. Lurie Comprehensive Cancer Center, is funded by the National Cancer Institute with the goal of applying physical sciences approaches to understanding the fundamental principles underlying aberrant gene expression in cancer.

Pulitzer Prize-winning Author, Dr. Siddhartha Mukherjee, Lectures on the History of Cancer at Northwestern University

On May 1, 2012, nearly 600 guests from the Northwestern University and Evanston community gathered in the Ryan Family Auditorium to journey through the history of cancer with oncologist and Pulitzer-prize winning author, Siddhartha Mukherjee, M.D., Ph.D. Dr. Mukherjee is well-known for ambitiously tackling the 4,000-year recorded history of cancer in his first book, The Emperor of All Maladies: A Biography of Cancer. The book has been widely hailed by critics as an ambitious, important, and unique contribution to the history of the social and scientific responses to cancer.

Mukherjee regaled a captivated audience with vignettes from both his own work and those of historically significant characters of cancer research, illustrating the often surprising and seemingly antithetical origins of treatment and diagnosis. At times both humorous and weighty, Mukherjee’s talk highlighted the intricate nature of both cancer and its effect on patients’ lives. A lively Q&A session followed the talk.
Mukherjee is an assistant professor of medicine at Columbia University and a staff cancer physician at Columbia University Medical Center. In addition to the 2011 Pulitzer Prize in general nonfiction, “The Emperor of All Maladies” (Scribner, 2010) was named by The New York Times as one of the “10 Best Books of 2010.”
The free public lecture was offered by the Northwestern University Physical Sciences-Oncology Center (PS-OC) as part of an effort to enrich the intellectual life on campus and to engage the larger community in the discussion regarding the future of cancer research.
The PS-OC, one of 12 established nationwide by the National Cancer Institute in 2009, is a joint effort between the Chemistry of Life Processes Institute and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. As Mukherjee’s book illustrates, many of the most important breakthroughs in cancer research have arisen from discoveries outside of the field of cancer research.
Brought together through the PS-OC, physical scientists and cancer biologists from across the University are focused on genes and their role in cancer. The unique perspective of physical scientists broadens the lens with which the PS-OC addresses most fundamental questions regarding the regulation of gene expression in normal health and development and in cancer. A better understanding of these mechanisms could lead to better diagnostics and therapeutics as well as open up new directions for research.

Symposium to Celebrate Contributions of Jonathan Widom

EVANSTON, Ill. — Colleagues, friends and family of Northwestern University professor Jonathan Widom will gather at a special symposium Friday, March 16, to celebrate his life, creativity and scientific accomplishments. Widom died suddenly last year at age 55.

Widom, an expert in the field of chromatin biology, was the William Deering Professor of Molecular Biosciences in the Weinberg College of Arts and Sciences and principal investigator of Northwestern’s Physical Sciences-Oncology Center.

“It will be a fabulous day of science,” said Richard I. Morimoto, the Bill and Gayle Cook Professor of Biology in Weinberg and an organizer of the symposium. “Speakers will reflect intellectually and scientifically about the impact Jon and his work have had on them. He made his mark on a wide range of fields, such as physical biochemistry, genetics and molecular biology, and on the molecular basis of diseases, including cancer.”

Unraveling the Mysteries of Life: Recognizing the Life of Jon Widom” will be held from 9 a.m. to 4:30 p.m. at the James Allen Center, 2169 Campus Drive, on the Evanston campus. Attendees are welcome to attend all or part of the public symposium but reservations are required.

Leaders in the fields of chromatin biology and gene expression will focus on the biological consequences of Widom’s discoveries as well as discuss the ongoing work in his research group. (Chromatin is the combination of DNA and proteins that make up the contents of a cell’s nucleus.)

“Jon Widom is greatly missed as he was a wonderful colleague at Northwestern who always listened to the scientific questions of others and then offered thoughtful and knowledgeable advice, usually from a quantitative viewpoint,” said Robert A. Lamb, chair of the department of molecular biosciences. “His broad knowledge made him highly sought after by colleagues, and he was always most generous with his time.”

In his research, Widom focused on how DNA is packaged into chromosomes — and the location of nucleosomes specifically. The work has had profound implications for how genes are able to be read in the cell and how mutations outside of the regions that encode proteins can lead to errors and disease.

“Jon’s contributions to the fields of chromatin packaging and gene regulation are unquestioned and reflected in his outstanding international reputation,” said colleague Kelly E. Mayo, professor of molecular biosciences.

Symposium speakers include Eran Segal of the Weizmann Institute of Science in Israel discussing “The Genomic Code for Nucleosome Positioning” and Northwestern’s Kristin Brogaard of the Widom lab discussing “A Chemical Biology Approach to Mapping Nucleosomes at Base Pair Resolution.” Other speakers whose research was influenced by Widom’s discoveries are: Carl Wu from the National Cancer Institute, John Lis from Cornell University, Barbara Meyer from the University of California at Berkeley and David Shore from the University of Geneva.

Jonathan Widom’s parents and siblings will attend the event. His brother, Michael Widom, of Carnegie Mellon University, is chair of the session “The Dynamic Interplay of Transcription Regulation and Chromatin Structure.”

Q-and-A time will allow for audience interaction with the speakers.

Sponsors of the symposium are the Office of the Provost, Weinberg College of Arts and Sciences, Chemistry of Life Processes Institute, department of molecular biosciences, the Physical Sciences-Oncology Center and the Cellular and Molecular Basis of Disease and the Molecular Biophysics training programs.

For more information, a schedule and to RSVP, go to the symposium’s website.

 

Article written by Megan Fellman, science and engineering editor for NU NewsCenter. Contact her at fellman@northwestern.edu.

Dr. Mary Hendrix awarded AACR Princess Takamatsu Memorial Lectureship

Dr. Mary Hendrix, President and Scientific Director of Children’s Memorial Research Center and NU PS-OC Project 4 team member, is the American Association for Cancer Research’s sixth annual recipient of the Princess Takamatsu Memorial Lectureship.  Dr. Hendrix will deliver her lecture, entitled Targeting the Pasticity of Metastatic Tumor Cells, on Monday, April 2nd at 3:30 p.m. at the 2012 AACR Annual Meeting (Chicago, IL).

For more information on the award and the AACR Annual Meeting, please visit: http://www.aacr.org/home/scientists/scientific-achievement-awards/takamatsu-lectureship.aspx

Breakthrough in Early Cancer Detection

EVANSTON, Ill. — “Early detection is probably the only way for us to win the war against cancer,” says Northwestern University’s Vadim Backman in a Science Nation video featured this week by the National Science Foundation.

Backman has been developing a suite of novel optics technologies with the goal of making early detection cheaper, more accurate and less invasive for an array of cancers. His longtime collaborator, Hemant K. Roy, M.D., of NorthShore University HealthSystem, has been leading clinical trials at Evanston Hospital testing the technologies on colon and lung cancers. The results have been promising.

“With this probe, we’ve probably done a couple of hundred patients. We’re about 90 percent accurate,” Roy says of the technology being used in the lung cancer study. “I think if this works, we could really make a big difference in how we treat patients.”

Backman is a professor of biomedical engineering at the McCormick School of Engineering and Applied Science, and Roy is director of gastroenterology research at NorthShore.

Backman’s pioneering approach looks at the tissue structure and composition of cells harvested from areas near organs that could develop malignancies. For example, cheek cells are harvested as a pre-screener for lung cancer, and cells harvested from just inside the rectum can be analyzed for potential colon cancer.

The researchers shine light on the harvested cells and analyze the signals provided by the photons bouncing off different structures within the cells. Highly sensitive forms of microscopy, the technologies can detect even subtle abnormalities that could indicate problems elsewhere in the body. Such prescreening could identify the individuals who would likely benefit from more invasive and expensive tests versus those who don’t need additional tests.

Backman and Roy soon will start a new clinical trial using biophotonics to screen cervical cells for signs of ovarian cancer.

Article written by Megan Fellman, science and engineering editor for NU NewsCenter. Contact her at fellman@northwestern.edu.

Thomas V. O’Halloran Named Center’s New Principal Investigator

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Thomas V. O’Halloran, PS-OC Principal Investigator

Thomas V. O’Halloran, PhD, has been named the new principal investigator for the Northwestern University Physical Sciences-Oncology Center. Widely regarded as a visionary scientist and talented builder of multidisciplinary research teams, O’Halloran played a crucial role in the formation of the Center and has sat on its advisory council for the past two years. In his new position as the Center’s scientific leader, Dr. O’Halloran fills a void left by the death of the PS-OC’s founding principal investigator, Jonathan Widom, who suffered a fatal cardiac arrest last July.

A Northwestern faculty member since 1986, Dr. O’Halloran has established deep connections to the university’s physical sciences and cancer research communities. He is the founding director of the Chemistry of Life Processes Institute, serves as associate director of basic science research within the Robert H. Lurie Comprehensive Cancer Center, and holds an appointment as the Morrison Family Professor of Chemistry.

Dr. O’Halloran’s research interests center on the regulatory biology and chemistry of transition metal receptors involved in homeostasis and oxidative stress pathways. His laboratory studies molecular mechanisms regulating the uptake, trafficking and utilization of metals essential for growth and proliferation (i.e. zinc, copper and iron); nanoscale drug delivery mechanisms; and the mechanisms of clinically important anticancer agents that are based on arsenic, molybdenum and platinum chemistry. This work provided early insights into molecular regulatory mechanisms and has led to the discovery of new classes of soluble metal receptors such as metalloregulatory and metallochaperone proteins. Most recently, he has discovered nanoscale processes for targeted delivery of multifunctional therapeutic agents capable of treating hematological cancer and solid tumors. These agents are moving rapidly towards clinical trials.

Remembering Dr. Jonathan Widom: Tributes and Condolences

Following the sudden death of Dr. Jonathan Widom, the Physical Sciences-Oncology Center has received many messages of sorrow and support from across the Northwestern community, the PS-OC network, and beyond. Assembled below are a series of reflections on Jon’s life and passing. This collection will be updated as the Center receives new messages in remembrance of a visionary scientist, respected colleague, generous mentor, and loyal friend.

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Dear Colleagues,

I am tremendously saddened to let you know that Professor Jon Widom passed away this afternoon following a massive cardiac arrest. His passing was quick and painless, and the doctors assure us that everything possible was done for him, but that the damage was just too severe.

This is shocking and terribly distressful news for all of us, and it will take a long time for us to come to grips with this loss. Our immediate thoughts and prayers are with Jon’s family and with his laboratory and close co-workers, and we offer them our condolences. I do not yet have any information on services or arrangements, and will hopefully be able to share more information about that with you tomorrow.

Jon will be remembered as an extremely creative and thoughtful scientist, able to seamlessly blend the biological questions he so passionately pursued with his broad background in chemical principles and quantitative analysis. His contributions to the fields of chromatin packaging and gene regulation are unquestioned, and are reflected in his outstanding international reputation and many awards and honors. I am certain that many accolades regarding Jon’s research contributions will pour in over the next days.

But to us, his colleagues, Jon was much more than an outstanding scientist. He will be remembered as a warm and caring friend, and as a dedicated mentor who always gave credit to his “troops”. He will be remembered for his love of opera, and travel, and good food and coffee, all best shared with the company of others. And for his gentle but sometimes very blunt humor. He will be remembered as a wonderful colleague who gave freely of his time, advice and expertise. And he will be remembered for serving the department and Northwestern with great distinction in many capacities, including his long tenure as chair.

At times like this, we are reminded that a department such as ours is truly a family, and that we must rely on one another and support one another under these difficult circumstances. I will be back in touch as I have more information.

With sadness,

Kelly

Kelly E. Mayo
Department of Molecular Biosciences
Center for Reproductive Science
Northwestern University

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Dear Colleagues,

It is with terrible sadness that I must inform you that Jon Widom passed away today.

Jon was an irreplaceable friend and colleague, and an intellectual tour de force, whose loss leaves an enormous hole in the graduate program and in the department.

This loss will be hard for all of us, but most of all for his laboratory – his troops as he lovingly called them – they were his family, and they meant the world to him.
Many of you have already been offering Jon’s lab what support you can – I thank you for this and I know that you will continue to do so in the coming days.

The graduate program and the department will support them, and all those touched by this loss, in any way necessary. There are clearly many hard days ahead for us all.

Kelly Mayo and/or I will let you know the details once there is information about a memorial service for Jon I paste a note from Kelly below as he speaks of Jon much more eloquently than I can muster at the moment.

Until then, I am very sorry to have to relay such terrible news via email

Sincerely,
Carole

Carole B LaBonne
WCAS Molecular Biosciences
Northwestern University

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Dear Weinberg Faculty and Staff:
It is with great sadness that I write to share with you the news that our colleague, Professor Jonathan Widom, passed away suddenly on Monday afternoon from an apparent heart attack. At his death, Jonathan was the William Deering Professor of Molecular Biosciences and Chemistry, as well as Director of the Keck Biophysics Facility.
Jonathan joined Northwestern in 1991 as Associate Professor in BMBCB and Chemistry. He subsequently served as BMBCB Department Chair for six years, from 1998 to 2004. His other service to the University included lengthy terms as Director of the Molecular Biophysics Training Program and as Director of the Center for Structural Biology. Jonathan’s distinguished research was focused on developing a concrete mechanistic understanding of gene regulation. His lab worked to understand how specific proteins or protein assemblies, acting in accord with the laws of physical chemistry, recognize and gain access to their DNA target sites in chromatin; and, conversely, to understand how the nucleosomal organization of chromatin and higher order chromatin folding modulate the action of these proteins and assemblies.
We will sorely miss Jonathan’s many contributions to the College and his field at large.
Please join me in expressing our deepest condolences to Jonathan’s family, friends, colleagues, and students. We will share additional information with you at a later time, including details about funeral/memorial arrangements.
Regards,
Sarah

Sarah C. Mangelsdorf
Weinberg College of Arts and Sciences
Northwestern University

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Dear Northwestern PSOC Trainees,

It is with great sadness that I write to inform that our leader and mentor, Professor Jonathan Widom, passed away suddenly on Monday afternoon from an apparent heart attack.

We have lost not only a scientist of great intellect and achievement but a most valued member of our community. Jon’s rigorous approach to questions of great importance has informed the ethos of our Center as has his passion for actually engaging in research and his impatience with bureaucracy and all its trappings.

I’m sure that you’ll join me and the PSOC staff in offering our support and condolences to Jon’s “troops”. Planning for a memorial service is underway and details will be posted on the NU-PSOC website as they become available.

With sadness,
Sheila

Sheila Judge
NU-PSOC

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Sheila-
I had heard the terrible news this morning. I am very sad. He was a special man. Please do keep me current on memorial activities etc. He was supposed to come to a chromatin meeting at the NCI in November and I will make sure we will have a remembrance for him here on that occasion.

Best wishes,
Tom

Tom Misteli,
National Cancer Institute
PSOC External Advisory Committee

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Dear Sheila

This is very sad news. Jon L told me this morning, and it is hard to believe. He was still young and in the most productive stage of his career. My condolences to his family, and to his extended family of students and colleagues.

Kevin

Kevin White
University of Chicago
PSOC External Advisory Committee

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I would like to add my deepest condolences and sadness on this tragic loss.

Noshir

Noshir Contractor
Northwestern University
PSOC External Advisory Committee

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This is shocking and sad news.
I saw Jon at lunch on Friday and he seemed full of vitality.
He will be sorely missed.

–Uri

Uri Wilensky
Northwestern University
PSOC External Advisory Committee

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Dear Sheila,

Please accept and extend my sincere condolences. What a tragic loss. It is difficult to believe.

Kathy

Kathleen Cook
Northwestern University
PSOC External Advisory Committee

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Thanks much Sheila,

I am in shock like many of us.
Where on the site are you going to post them?

Thanks

Marcus Peter
Feinberg School of Medicine
Northwestern University

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Dear Sheila,

I was shocked by this news. It’s so sad. In my eyes, Jon is a very kind, warm-hearted, and modest colleague and friend. I prayed for him this morning and want to pray for him in our Sunday service. Do you know what religion he has? I also look forward to hearing from you what we can do to help his family.

My thoughts and prayers are with you, his family and friends. Love.

Jindan

Jindan Yu
Feinberg School of Medicine
Northwestern University

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It was a profound privilege for the Hendrix laboratory to work with Jon on the PSOC project. His brilliant insights instigated novel scientific avenues of exploration. His humble, genuine demeanor is a legacy we shall all remember. Thank you to Jon for including us in his extended scientific family. We are forever grateful for the research time we shared together.

Mary Hendrix, Elisabeth Seftor and Richard Seftor

Children’s Memorial Research Center
Children’s Memorial Hospital
Northwestern University

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I am so so sorry to hear that. He will be sorely missed. Please dont hesitate to contact me if there is anything at all I can help with.

Franziska Michor
Harvard University

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Dear Sheila,

Sorry for not replying sooner as I’m out of the country. I was utterly shocked when I read the news this morning about the loss of Jon.

On behalf of the Office of Physical Sciences – Oncology staff, I would like to express our deepest sympathy to his family, his PS-OC team, and lab members. His contribution to science was tremendous and his latest venture to bring physical sciences to oncology will be truly missed. His love of science, deep insight, and ability to bring high quality people together has always been some of his hallmarks and something that all of us in the PS-OC Network strive to achieve.

Again our condolences to Jon’s family and please let know if we can assist in anyway.

With deepest respects,
Larry

Larry A. Nagahara
Office of Physical Sciences – Oncology
National Cancer Institute

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Sheila, NU PS-OC Members, and Widom Lab,

I was shocked and saddened to hear of Jon’s passing. I have admired and been inspired by his science for years. His contributions to chromatin organization and gene regulation influenced my own work as a graduate student and postdoc. As I have worked with Jon over the past couple of years and come to know him personally I have gained an admiration for him as a person as well. He was kind and friendly, always taking the time to say hello or introduce me to colleagues when we crossed paths. He will be greatly missed. My thoughts and prayers are with all of you and with Jon’s family.

Warm wishes,
Sean

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Dear Sheila and Jonathan,

This does indeed hit hard. It is impossible to express the sadness and shock that comes with the news of Jon’s passing. Please do send our condolences to Jon’s lab and let us know what we can do to keep his mission alive.

With kind regards
Peter and Kelly, for the Scripps team

Peter Kuhn and Kelly Bethel
The Scripps Research Institute PS-OC

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Dear Sheila,

What a terrible loss! I knew Jon for several years. Please accept my most sincere condolences, and pass them to Jon’s colleagues.
Thank you for letting me know and please keep me posted as I’ll try to attend the memorial service.

— Leonid

Leonid Mirny
Massachusetts Institute of Technology

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Dear Sheila,

I too would like to express my deepest condolences to Jon’s family, laboratory and colleagues. It is clear from the remembrances that we all feel the tremendous loss of such an esteemed thinker, mentor and friend.
As being just a few years older than Jon and starting out in chromatin myself, I followed his work with great joy and anticipation for a good quarter of a century. He was one of my role models for the sheer beauty of his logic and execution of complex experiments. He was one of the true icons in the field. There are very few of us that can say science would be worse off in our absence. The scientific community has lost a rare hero and inspirational leader.

Kerry Bloom
Thad L. Beyle Distinguished Professor
Dept. of Biology
University of North Carolina

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To all of those who knew Jon Widom,

I write with you all to express my most sincere and deep sympathy over learning yesterday of the tragic passing of Jon. My sadness and shock is beyond words. I will not be able to ease your pain; I write only as a chromatin biochemist who had the deepest respect for Jon as person, scientist and leader of our field. From my early interactions with Jon, I was taken back by his smarts and his deep insights into the biophysical properties of chromatin particles, arrays and beyond. As I got to know him better, I became equally impressed with his comfort and clear understanding of chromatin biology.

I have several fond memories of Jon that I would like to share with you. First, I bumped into Jon by accident on the Rockefeller campus shortly after I moved there. Surprised to see him, I invited Jon up to First Avenue to grab some lunch where I was surprised to learn that he was in New York City, working with Eran Segal on what went on to become landmark studies on nucleosome positioning. It was a fun lunch, and it was clear to me then how fun Jon was having in NYC; we had many good laughs, and as was typical, Jon asked me several great questions as to what we were doing in the lab. Second, Jon came back to NYC a couple of years later to be our chosen featured speaker at one of our Leukemia-Lymphoma SCOR grant annual meetings, lead by Jon Licht. It was a delightful lecture, packed with Widom chromatin insights, peppered with Widom humor. Finally, I was fortunate to give one of the opening-night lectures with Roger Kornberg at a wonderful Keystone Chromatin/Transcription meeting in Taos, NM in January, 2010, organized by Jon, Geeta Nalikar and Dinshaw Patel. I have attended many terrific chromatin meetings at various stages of the chromatin field’s history, but this meeting was one of my recent favorites. Why? It has a clear imprint of its organizers – it had lots of terrific biophysical, structural and enzymological talks and posters, and much less chromatin biology than I was used to. It was a wonderful meeting – in short, it had a ‘Widom feel’ to it. Unfortunately, I had not seen Jon since that meeting.

In closing, I will miss Jon – his many gifts and talents were clear; he will be missed by all of us, but not forgotten. I have a huge amount of respect for what Jon and his colleagues have done for our field; their scientific contributions have been enormous and remarkable. But the older I get, the more I recognize that Jon was a very special person — decent, fun and caring, a good mix for all of us to aspire to.

With genuine sadness and sympathy,

David Allis

Joy and Jack Fishman Professor
Head, Laboratory of Chromatin Biology and Epigenetics
The Rockefeller University

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Dear Sheila,

This is truly terrible news, Jon will be tremendously missed within the field of chromatin biochemistry and in science as a whole. I cannot imagine the devastating impact this loss will have at the PSOC, NU, his lab, and for is family. My deepest condolences. If we can be of any assistance helping Jon’s lab through this difficult time, please let me know.

Best,

Alex

Alex Ruthenburg
University of Chicago

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Sheila, Please let Jon’s family and his staff know of my great sadness and sympathy for their terrible loss.

Jon was a visionary. His work was so important to us as we shaped the concept for the PSOCs; and his subsequent leadership as a senior member of the PSOC network was exemplary. He was a man of great ideas and high standards – and we are all better for having known and worked with him. Jon made remarkable contributions to the PSOCs (and broadly to cancer research and science) and touched lives in ways that will be with us always. He will be greatly missed!

My condolences to Jon’s family – and please share any suggestions for where donations in his name might be directed.

Respectfully, Ann Barker

Anna Barker
NCI Center for Strategic Scientific Initiatives, NIH

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Sheila and Jon,

I would like to echo Ann’s sentiments and apologize for not writing sooner as I am currently at our annual NCI Budget Retreat. I had a good phone conversation with your Cancer Center leadership and let him know how much Jonathan’s leadership and expertise meant to this Network. I am honored to have worked with him only on a few things and he will be missed.

Please convey my condolences to the Widom lab and family.

Jerry

Jerry S.H. Lee
Center for Strategic Scientific Initiatives (CSSI),TCGA Program Office
National Cancer Institute, NIH

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Dear Sheila,

Sean just informed me that Jon Widom has suddenly passed, and I am in shock and devastated. Please accept my deepest condolences. You and your entire team at Northwestern and Jon’s family are in my thoughts and prayers. May peace be with you during this difficult time.

Best wishes,
Nas

Nastaran Zahir Kuhn
Office of Physical Sciences-Oncology
National Cancer Institute, NIH

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Thank you, Sheila. What a terrible shock (!), and how incredibly sad. We take pause to reflect and remember this loss.
Best,
Rich

Richard E.B. Seftor
Northwestern University
Children’s Memorial Research Center

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Hello Sheila,

I am so shocked to hear the news. I want to share the deepest sadness to lose Jon. Please let me know if there is anything I can do to support and deliver our sympathy to his family and lab members. May your memories with him be your comfort.

With deepest sympathies,
JooSang Lee
Northwestern University

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Dear Dr. Judge and the Widom lab,

I want to express my heart-felt condolences at the tragic death of Jon Widom. I worked with Jon as a post-doctoral fellow shortly after his arrival at Northwestern. He was an extraordinary mentor who taught me not only the nuts and bolts of chromatin biochemistry but also invaluable lessons about being a thoughtful and generous scientist. He was a truly unique person in our field and he will be sorely missed. If I can be of any assistance in this difficult time, please do not hesitate to contact me.
Mark Parthum
Department of Molecular and Cellular Biochemistry
Ohio State University

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The personnel of the Keck Biophysics Facility is devastated by the loss of its Director, Dr. Jonathan Widom.
Dr. Widom established the Keck Facility in 1997 with funding from the W. M. Keck Foundation, the NIH and the Rice Foundation. He was passionate about constantly bringing in new techniques and state of the art instrumentation; he viewed the facility as a unique academic resource where not only equipment but also expertise and ideas can be shared. Under his leadership the Keck Facility became one of the major core laboratories of the Lurie Cancer Center and was repeatedly recognized by the Office of Research as one of the outstanding core facilities at Northwestern.

We feel privileged to have had the chance to work with Jon and know him closely. His leadership and expertise were exceptional. His kind mentorship, wonderful advice, warm and caring personality will be thoroughly missed.

Arabela Grigorescu
Manager | Keck Biophysics Facility
Northwestern University

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I just received word of Jon’s untimely death. He was a good friend dating back to our days at UIUC. There are undoubtedly a huge number of colleagues worldwide that are, or will be, shocked by his passing. He was very kind and funny, in addition to being incredibly intelligent. He has left an important scientific contribution to be sure. But in addition he was a good friend to many of us and we will miss him.

Sincerely
Cathy Royer
Directeur de Recherche
Centre de BiochimieStructurale
Montpellier France

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I knew Jon for a long time, our paths crossed at many meetings and we shared common interests in biological physics. Jon had excellent taste in problems that had both strong physics content and biological impact, that is a rare quantity. I didn’t always agree with Jon, he was a strong personality and so am I, so we had our share of battles. In the end we were friends, and I was glad to see him become an important part of the Physical Sciences Oncology effort. He left us far too soon.

Assuring you of our best attention at all times, we beg to remain dear Madame or Sir, yours very truly:

Robert H. Austin
Department of Physics
Princeton University

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Dear Sheila,

I was shocked, dismayed and deeply saddened to learn this terrible news. (I saw the ambulances and paramedics around Cook Hall Monday afternoon, but little did I realize what that was all about…)

So much is already said about Jon and I echo all our colleagues’ sentiments. Jon was a good friend and a learned colleague. He was also an “advisor” and confidant to me and our NUANCE staff on many fronts; particularly in our collective aspirations to develop bio-cryo microscopy capabilities to address emerging opportunities in ultrastructure analysis of “soft” matter such as DNA/Chromatin. Just as we are about develop some unique ways to image and analyze DNA and chromatin patterns, we will terribly miss his insights, advice and friendship. It is so sad and shocking that I am at a loss to express it in mere words. Alas..

Our most heartfelt condolences to his family, friends and his students/group members.

Warm regards,
Vinayak & NUANCE Center colleagues

Vinayak Dravid
Professor of Materials Science & Engineering
Director of NUANCE (Northwestern University Atomic and Nanoscale Characterization Center)
Northwestern University

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It was a terrible shock to hear of Jon Widom’s premature death. Although I only met Jon a few times, he made a great impression on me, and I often mentioned him to others as a role model of excellence in science, both in terms of his work and the way he conducted himself. He presented a seminar in our ASU Biophysics Seminar series some years ago, and it still stands in my memory as the best talk we hosted over an eight year period. It is a tragedy that he has left us so soon.

Timothy Newman
Professor of Biophysics
University of Dundee
Scotland

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Please accept our condolences— although I did not really know Jon, I do know his father as a colleague here. Such events and times are always difficult. Best wishes to you and your colleagues in your PS-OC and at Northwestern through these difficult days

Mike Shuler
Physical Sciences-Oncology Center
Cornell University

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I am deeply saddened to hear the news. Jon has been extremely supportive during the first years of my independent career, and I consider myself tremendously fortunate to have had the chance to collaborate with him. Jon has been, and will continue to be, an incredible role model. His generosity, humility, and scientific genius has touched my life in many ways, and his death will leave a void that will be felt for many years to come.

Marcia Levitus
Arizona State University

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jw_corsica.jpgDear Colleagues,

It was with great sadness that I heard about the death of Jon Widom.

I wish to share with you in memory a photo taken in 2006 in Corsica, France where Jon came to give several lectures at a summer school on DNA and Chromosomes that I organized. The photo is not very good, but this is how I like to remember Jon, enjoying himself during a boating excursion whilst in deep discussion with his good friend, Bill Gelbart. Jon added a memorable contribution in 2006 to the success of the summer school, and his death affects us all.

Sincerely,

Alan Braslau
CEA DSM-IRAMIS-SPEC
FRANCE

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My condolences on Northwestern’s recent loss. I was honored to meet Dr. Widom and was completely floored by his warmth and intellectual tenacity. I distinctly recall one comment he made during our dinner conversation: when asked if he had any children, he responded with “My students are my children.” It was then that I realized how unique Dr. Widom really was. I am at a loss for words and dumbfounded, as others are, by the abrupt manner of his passing. I offer my deepest condolences to Dr. Widom’s family, the lab, and to his colleagues. He will be missed here at Caltech where he was a dear friend of the Phillips group.

Sincerely,
Pradeep Ramesh
California Institute of Technology

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It comes as a shock when the world loses one of its great scientists, this tragedy is compounded when this scientist was also a great human being- Jon Widom was both of these things. I first met Jon in 1987 when I spent a month-long rotation in his laboratory at the University of Illinois at Urbana-Champaign as part of an inter-departmental program in molecular biology. Jon himself was the epitome of the multi-disciplinary approach, at the time he held appointments in three different departments: Chemistry, Biochemistry, as well as Biophysics. Working in his lab, it soon became apparent to me that no single discipline could house Jon’s expansive ideas- it was also apparent that my search for a scientific mentor had come to a successful end.

Jon had all of the qualities one could ask for in an advisor- he had a seemingly infinite amount of patience as well as an infectious enthusiasm for science. Before joining his laboratory, I had thought very little about chromatin structure and function, but now it has become a life-long passion for me. I have also tried to emulate some of the qualities that I most admired in Jon- I think that I am an exceedingly patient person at least in part due to his influence. I have also tried to pass on an enthusiasm for learning to my own students in my role as a professor at a small liberal arts college. Although my own educational training did not take place at such an institution, I found that the multi-disciplinary approach emulated by Jon helped to prepare me to embrace a wide-range of subjects beyond the realms of molecular biology.

I never questioned Jon’s motivation for pursuing science. He wasn’t interested in fame or recognition, he wasn’t out to prove others wrong- he simply loved research for the thrill of discovery. When he accepted a position at Northwestern University, I, along with the other members of his laboratory at that time, knew that he didn’t have only himself in mind when making such career decisions. We trusted Jon’s inclination completely- none of us thought for long about not following him to Evanston, Illinois.

Jon put a lot of thought into everything that he did. When I asked him any question, even a seemingly innocuous one, Jon would pause (sometimes for a somewhat uncomfortable amount of time), while he formulated a precise answer. Jon’s research was impacted by this philosophy in life- he performed careful, meticulous work that he had thought deeply about before beginning. He claimed that he had obtained some of his propensity for careful thought during his postdoctoral studies with Aaron Klug at the MRC in Cambridge. He often spoke of long discussions that would take place with scientists from a number of disciplines over tea, followed by long evenings performing the experiments that had been vetted in this way.

One pet peeve of Jon’s was unnecessary verbosity; he taught me that being concise was always the best approach. He would tell me “The chance of someone reading something that you have written is inversely proportional to its length.” I hope to have put into practice everything that I have learned from Jon.

James Godde
Professor and Chair of Biology
Monmouth College

In Memoriam: Dr. Jonathan Widom

It is with profound sadness that the Northwestern University Physical Sciences-Oncology Center announces that our leader, colleague, and mentor, Professor Jonathan Widom, passed away suddenly on Monday afternoon following an apparent heart attack. At the time of his death, Dr. Widom was the William Deering Professor of Molecular Biosciences and Chemistry at Northwestern, the Director of the NU Keck Biophysics Facility, and the Principal Investigator for the PS-OC.

With Dr. Widom’s passing, we have lost both a major intellectual force and a valued member of our community. Jon’s rigorous approach to scientific questions of fundamental importance informed the ethos of our Center, and his passion for research served as an inspiration to his friends, colleagues, and students. A scientist of the highest caliber, Jon earned substantial international recognition for his work on chromatin packaging and gene regulation. Yet his personal modesty and exceptionally high standards prevented him from taking much credit for his outstanding contributions. Rather than seeking the spotlight for himself, he preferred instead to serve as a dedicated and generous mentor who enthusiastically praised the talents and contributions of all who worked with him.

Jon is survived by his parents, Ben and Joanne, of Ithaca, NY, and a brother and a sister. Burial will be private but condolences may be sent to: The Widom Family, 204 The Parkway, Ithaca, NY 14850.

Donations can be made to Northwestern University to endow the “Jonathan Widom Lectures in Molecular Biosciences.”  Checks should be payable to Northwestern University in honor of Jonathan Widom and mailed to Catrina Dagostino, senior director of development, Weinberg College of Arts and Sciences, Northwestern University, 2020 Ridge Ave., Evanston, IL 60208-4308

Online donations may be made at www.giving.northwestern.edu. Select “Make a Gift”, then under “My Designation” enter “In honor of Jonathan Widom”. For further information contact cdagostino@northwestern.edu (847) 491-4583.

Donations can also be made to the Lyric Opera of Chicago http://www.lyricopera.org/support/donate.aspx
Please specify this is a commemorative gift in honor of Jonathan Widom.

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