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Program in Systems Biology News

The Program in Systems Biology Welcomes our Newest Rotation Students

September, 2021

Gavin Birdsall - Joins the Lee Lab for Rotation

Vista Sohrab - Joins the Mitchell Lab for Rotation

Carmen Li - Joins the Shank Lab for Rotation

Lauren Intravaia - Joins the Walhout Lab for Rotation

Bradley Class Joins the Youk Lab for Rotation

The Mitchell Lab Welcomes Sydney Schock (GSBS Student)

September, 2021

The Youk Lab Welcomes Helen Magana (GSBS Student)

September, 2021

The Dekker Lab Welcomes Jiangyuan Liu (GSBS Student) and Xiangru Huo (Bioinformatician)

September, 2021

Congratulations to Michael Lee

June, 2021

Michael Lee received a 22 month sponsored research agreement with Hillstream Biopharma. The project is titled “Chemo-genetic profiling to identify mechanisms of action and genetic determinants of sensitivity for novel chemotherapeutics” and this collaboration isto determine the mechanisms of action and chemo-genetic interactions for their novel compound.

Congratulations to Nicola Minchell on The Marie Curie Global Fellowship!

January, 2021

We Welcome Nicola Minchell, Visiting Scholar From the University of Cambridge, UK, to the Dekker Lab and Program in Systems Biology

January, 2021

We welcome Rachel Walker, Research assistant, to the Youk Lab and Program in Systems Biology

January, 2021


Rachel is from Lancaster, MA. She graduated from Brown University, where she studied Biomedical Engineering as an undergraduate. As a Worcester County native, Rachel was lucky enough to get a glimpse of the life of a researcher in high school, when she had an internship over spring break at UMass Medical School itself. That very first experience in a lab sparked a passion for research, and Rachel is excited to begin her professional career at the institution that inspired her. In her spare time, Rachel enjoys reading, puzzles, and scuba diving.

Congratulations to Dr. Elizabeth Shank on Receiving Tenure

January, 2021

Hyun Youk, PhD, has received the CIFAR AI Catalyst Grant

November 2, 2020

This grant will support of his collaborative project, “Mechanisms of bacterial spatial localization in response to oxidative stress in the gut.”This is a joint award with Professor Carolina Tropini, School of Biomedical Engineering, University of British Columbia.

Hyun Youk, PhD, has been selected as a member for the EMBO Young Investigator Programme

November 2, 2020

EMBO identifies and supports some of the best young researchers in the life sciences. EMBO Young Investigators are group leaders in the early stages of setting up an independent laboratory and the programme helps them develop skills and connections that will help them during this career stage.

Hyun Youk, PhD, joins the Program in Systems Biology

November 2, 2020

Dr. Hyun Youk

We welcome Dr. Hyun Youk to UMass Medical School as an Associate Professor in the Program in Systems Biology. Hyun and his lab study how living systems transition between being alive and being either truly dead or seemingly dead. They hope to discover common, quantitative principles that underlie life or death transitions. The Youk Lab is particularly eager to unveil principles that allow life to be restarted after it has nearly ceased. Their studies use microbes and mammalian cells (e.g., yeasts and mouse embryonic stem cells), and combine experimental approaches, mathematical models, and ideas rooted in statistical physics to achieve their goal.

Despite the remarkable advances in science, "what is life?" is a long-standing, deceptively simple-to-state question that still remains difficult to address at a deep level. The same is true for the related questions, "what is death?" and "can we revive any dead things?". Every molecule in a cell (e.g., DNA, RNA, protein) is governed by the same laws and principles of physics and chemistry as non-living systems. Yet, unlike non-living systems such as rocks and metals, biomolecules can interact amongst themselves to somehow endow a cell with "life" and all the remarkable behaviors associated with a living state (e.g., making decisions, processing information, cognition). Microscopic cells, too, can interact amongst them to endow life to macroscopic beings. How does a state of living emerge from interacting molecules and cells? The Youk Lab hopes that their work can reveal how small and large-scale networks of molecules and cells engender life, death, and revival. Beneath the molecular mechanisms that are specific to each organism, they believe that there may be quantitative principles that are common to many different cell types and organisms.

Welcome to the PSB!

UMMS scientists to expand 4D nucleome research with $13 million NIH grants

Job Dekker and Paul Kaufman to investigate architecture of genome as it changes over time

October 23, 2020
By Jim Fesseden                                                                                       
UMass Medical School Communications
Job Dekker, PhD and Paul Kaufman, PhD

Investigators at UMass Medical School have received two, five-year grants totaling $13 million to explore how the 4D genome structure influences gene expression, cellular function, development and disease as it reshapes itself over time. The Center for 3D Structure and Physics of the Genome, led by Job Dekker, PhD, will receive the bulk of the funding—approximately $11 million. Paul D. Kaufman, PhD, will receive $2 million to investigate the role of the nucleolus in human genome organization in normal and disease states.

The grants are part of the NIH’s 4D Nucleome Program, an interdisciplinary effort launched in 2015 comprising 30 research teams across the country with the goal of mapping the three-dimensional architecture of the human genome and how this organization changes over time—the fourth dimension. The goal is to understand how 4D genome structure influences gene expression, cellular function, development and disease.

“The first phase of the project revolved around developing new technologies and techniques that we could use to explore the structure of the genome in time and space,” said Dr. Dekker, Howard Hughes Medical Institute investigator, the Joseph J. Byrne Chair in Biomedical Research, professor of biochemistry & molecular pharmacology and co-director of the Program in Systems Biology. “This new center study will investigate how the genome folds across human lifespan starting from the early pluripotent stem cell state to later stages when cells age.”

Job Dekker elected to European Molecular Biology Organization

July 07, 2020

Dr. Job Dekker

The European Molecular Biology Organization (EMBO) has elected Job Dekker, PhD, Howard Hughes Medical Institute investigator, the Joseph J. Byrne Chair in Biomedical Research, professor of biochemistry & molecular pharmacology, and co-director of the Program in Systems Biology, to lifetime membership in the organization. Dr. Dekker and 62 other leading scientists from around the world were elected in recognition of their remarkable achievements in the life sciences.

“The new members have contributed to the success of research in the life sciences in Europe and around the world,” said EMBO Director Maria Leptin. “As EMBO members, they can help to shape     the future through EMBO’s work to support talented researchers, bring ideas together, and   promote an international research environment conducive to excellent science.”

UMMS students produce hand sanitizer for nearby hospitals amid COVID-19 pandemic

April 10, 2020

In a time of dire need, as medical professionals are working to care for patients during the COVID-19 pandemic and critical supplies of protective gear are running low, students in the Graduate School of Biomedical Sciences at UMass Medical School produced nearly 130 gallons of hand sanitizer in less than three days to help sustain local hospitals. 

“We wanted to find a way to get the graduate students involved in this effort,” said MD/PhD student Peter Cruz-Gordillo, a member of the UMMS COVID-19 student task force. “By the day, COVID-19 cases are increasing. There’s a great need for sanitizer not just for hands, but also to clean off the PPE. We thought this would be a great opportunity to help.”

Elizabeth Shank, PhD, joins the Program in Systems Biology

January 2, 2020

Dr. Elizabeth ShankPSB welcomes Dr. Elizabeth Shank to UMass Medical School as an Associate Professor of Microbiology & Physiological Systems. Beth and her lab study microbiolal activities and how they impact their hosts and ecosystem. They are particularly fascinated by the idea that microbes are able to generate and secrete chemical cues (specialized or secondary metabolites) that can act as interspecies signals to influence the physiology and metabolism of their microbial neighbors, and thus contribute to the stability and functioning of complex microbial communities.

The Shank lab's research dissects microbial interactions using traditional microbiology, fluorescent co-culture, bioinformatics, mass spectrometry imaging, and native-like microcosms. They aim to define the molecular basis of how microbial specialized metabolites impact bacterial cellular differentiation, discover chemical tools to kill and modulate pathogens, and dynamically visualize microbial interactions at the single-cell level. Their goal is to gain insights into microbial ecology as well as identifying novel bioactive compounds as potential therapeutics and chemical tools to achieve our long-term goal of manipulating microbial communities to improve host health and the environment.

Welcome to PSB!

Amir Mitchell to study cellular decoding of extracellular information with new NIH grant

October 9, 2019

Amir Mitchell, PhDAmir Mitchell, PhD, assistant professor of molecular medicine in the Program in Systems Biology, has received the Maximizing Investigators' Research Award from the National Institute of General Medical Sciences to support research into cellular decoding of signaling dynamics.

Dr. Mitchell will use the five-year, nearly $2.1 million grant to study how intracellular dysfunctions, as mutations, corrupt information encoding and which cellular processes need to be targeted in order to restore proper encoding.

“Healthy cells in the human body use temporal patterns of activity in signaling pathways to encode information about the extracellular environment. Many diseases, foremost cancer, stem from corruption of these temporal signaling patterns which culminates in maladaptive outcomes as uncontrolled cell proliferation,” Mitchell said.

Job Dekker receives the Chancellor’s Medal for Distinguished Scholarship at the 2019 Convocation

September 13, 2019

Job Dekker and Chancellor Michael CollinsJob Dekker, PhD, Howard Hughes Medical Institute Investigator, the Joseph J. Byrne Chair in Biomedical Research, professor of biochemistry & molecular pharmacology and co-director of the Program in Systems Biology, received the Chancellor’s Medal for Distinguished Scholarship. As recipient of the honor, Dr. Dekker will present the plenary lecture at the 20th Annual Research Retreat next month.

Chancellor Michael Collins (pictured right with Dr. Dekker) said Dekker was described by his peers as an “unselfish collaborator,” an “intellectual leader,” and as one who “inspires loyalty in his collaborators.”

Amir Mitchell lab engages high school classes in superbug research via online portal

May 14, 2019

Worcester Technical High School juniors in the Biotech Department took part in the innovative program developed by Amir Mitchell, PhD.

Under the guidance of Amir Mitchell, PhD, assistant professor of molecular medicine in the Program in Systems Biology, 250 high school students from Massachusetts, California and Israel have had the opportunity to research one of medicine’s biggest challenges today—the emergence of superbugs. While students often learn about strains of drug-resistant bacteria in school, Dr. Mitchell’s innovative program is allowing these students to conduct their own investigations into the phenomenon. Mitchell’s lab collaborated with Anat Yarden, PhD, of the Weizmann Institute of Science in Israel, to develop an approach to educate high school students on the emergence of antibiotics resistance through natural selection and rapid evolutionary adaptation. This year, Worcester Tech students (pictured left) were joined by peers in Brockton and San Francisco to monitor, in real-time through live video streams on YouTube and the project’s website, how drug resistance gradually emerged. The educational framework for this project was published in PLoS Biology.

Job Dekker and colleagues develop new model to examine large mutations in cells

September 11, 2018

Dekker Nature GeneticsScientists at UMass Medical School, Pennsylvania State University and Florida State University have developed a new computational framework combining three methods of finding large mutations in cancer cells into a single, more complete model. The new method, described in a study published in Nature Genetics, will help researchers find what are called “structural variants” within cancer genomes and learn more about how such cancers begin.

Each of the three methods alone only reveals a portion of the structural variations found in cancer cells, but when the results of all methodologies are integrated using the new model, a more comprehensive view of the genome emerges, said study authors Job Dekker, PhD, Howard Hughes Medical Institute Investigator, the Joseph J. Byrne Chair in Biomedical Research, professor of biochemistry & molecular pharmacology and co-director of the Program in Systems Biology at UMMS, and Feng Yue, PhD, assistant professor of biochemistry and molecular biology at Penn State.

Ben Landry, Mike Lee and colleagues publish their findings on the diversity in tumor-stromal cell interactions that modulate chemotherapeutic drug sensitivity in Molecular Systems Biology

June 28, 2018

Diagram of the experimental co-culture systemDue to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large‐scale coculture assay optimized to measure drug‐induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo‐insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested when these cells are cocultured with stromal cells, such as fibroblasts. Furthermore, we find that fibroblasts influence drug responses in two distinct and divergent manners, associated with the tissue from which the fibroblasts were harvested. These divergent phenotypes occur regardless of the drug tested and result from modulation of apoptotic priming within tumor cells. Our study highlights unexpected diversity in tumor-stroma interactions, and we reveal new principles that dictate how fibroblasts alter tumor drug responses.

PSB faculty receive award for outstanding contribution to curricular development for the Systems and Computational Biology course

Dr. Rob Brewster lectures students on using MatLab for image processing.

April 19, 2018

The faculty members of the Program in Systems Biology received an award for outstanding contribution to curricular development at the 20th annual Educational Recognition Awards ceremony. The Systems and Computational Biology course was cited for excellence in teaching concepts and ideas needed for modern biological analysis. All faculty members from the program contributed to the course development: A.J. Marian Walhout, PhD, Robert C. Brewster, PhD, Job Dekker, PhD, Michael J. Lee, PhD, Amir Z. Mitchell, PhD, and Lutfu Safak Yilmaz, PhD.

Job Dekker receives 2018 Edward Novitski Prize

February 9, 2018

The Genetics Society of America (GSA) has named Job Dekker, PhD, the recipient of the 2018 Edward Novitski Prize. The award honors investigators who have exhibited “an extraordinary level of creativity and intellectual ingenuity in the solution of significant problems in genetics research.”

Dr. Dekker, Howard Hughes Medical Institute Investigator, the Joseph J. Byrne Chair in Biomedical Research, professor of biochemistry & molecular pharmacology and co-director of the Program in Systems Biology at UMass Medical School, is recognized for scientific contributions that include the development of chromosome conformation capture—a technique that has revolutionized chromosome research.

Chromosome conformation capture, or 3C, allows researchers to study the interactions of chromosomes at resolutions and scales previously impossible to attain. In 3C, chromatin is treated with a crosslinking chemical that causes chromosomal regions that are near each other to be chemically linked together. By isolating these crosslinked regions of chromatin and determining their DNA sequences, geneticists can deduce which parts of the genome are in proximity to each other. Although the foundation of the technique seems simple, no one before Dekker had formulated a practical way to take advantage of it for a high-throughput molecular assay like 3C.

Study from the Dekker lab and colleagues answers 100-year-old question about how chromosomes get their distinctive X-shape

January 18, 2018

A multi-disciplinary team at UMass Medical School led by Job Dekker, PhD, has unraveled how chromosomes are packaged into their iconic X-shape during cell division. Packaging the genome inside mitotic chromosomes is critical to the faithful transmission of DNA from parent to daughter cells; these findings shed new light on the inner workings of cell division and may provide novel targets for potential cancer treatments.

“Cancer cells are experts at dividing. They do it well, and they do it very fast,” said Dr. Dekker, Howard Hughes Medical Institute Investigator, the Joseph J. Byrne Chair in Biomedical Research, professor of biochemistry & molecular pharmacology and co-director of the Program in Systems Biology at UMMS. “Many cancer therapies take advantage of this fact and attack dividing cells specifically in the hopes of eliminating the cancer. The more we understand about how this process works, the more ways we have to throw a wrench into this machine and disrupt this process.”

Job Dekker appointed inaugural Joseph J. Byne Chair in Biomedical Research

July 17, 2017

Job Dekker, Ph.D.Two newly established endowed chairs at UMass Medical School—the Joseph J. Byrne Chair in Biomedical Research and the Herman G. Berkman Chair in Diabetes Care Innovation—were approved by the UMass Board of Trustees on Monday, July 17, according to Chancellor Michael F. Collins.

Job Dekker, PhD, Howard Hughes Medical Institute Investigator, professor of biochemistry & molecular pharmacology and co-director of the Program in Systems Biology, and Michael J. Thompson, MD, clinical professor of medicine and chief of adult diabetes clinical research, were appointed to the positions, respectively.

The purpose of The Joseph J. Byrne Chair in Biomedical Research is to support the research activities of an accomplished faculty member whose work is advancing the fundamental understanding of human biological systems and offering new and innovative pathways to treat human disease. Dr. Dekker is one of the medical school’s most dynamic and cutting-edge researchers and is the inaugural holder of The Joseph J. Byrne Chair in Biomedical Research.

Aurian García-González, Marian Walhout, and colleagues publish study in Cell showing that bacteria modulate host chemotherapeutic drug responses

April 21, 2017

Marian Walhout, Ph.D., and MD/PhD student Aurian Garcia-GonzalezThe bacteria residing in your digestive tract, or your gut microbiota, may play an important role in your ability to respond to chemotherapy drugs, according to a new study by scientists at UMass Medical School. Published in Cell, the study by Marian Walhout, PhD, and colleagues shows that when a common research model, the roundworm Caenorhabditis elegans, was fed a diet of E.coli bacteria, the worms were 100 times more sensitive to the chemotherapy drug floxuridine (FUDR) than worms who were fed different bacteria. FUDR is a commonly used drug to treat colorectal cancer.

Cancer doctors have long been puzzled by how dramatically patients with the same disease can respond differently to the same treatment—even in cases where identical twins have the same diagnosis. “Two twins, genetically identical, who have colorectal cancer could potentially respond very differently to the same treatment because of their microbiome,” said Dr. Walhout, the Maroun Semaan Chair in Biomedical Research, professor of molecular medicine and co-director of the Program in Systems Biology. “If we can learn how bacteria affect the efficacy or toxicity of chemotherapies, it’s not hard to imagine developing personalized medicine built on probiotics that could improve the clinical benefits of some cancer treatments.”

Rob Brewster and colleagues publish a kinetic model of transcription that incorporates the interplay between transcription factor copy number and its binding sites in PLoS Computational Biology

April 17, 2017

Transcription Factors on PromotersGene expression is intrinsically a stochastic (noisy) process with important implications for cellular functions. Deciphering the underlying mechanisms of gene expression noise remains one of the key challenges of regulatory biology. Theoretical models of transcription often incorporate the kinetics of how transcription factors (TFs) interact with a single promoter to impact gene expression noise. However, inside single cells multiple identical gene copies as well as additional binding sites can compete for a limiting pool of TFs. Here we develop a simple kinetic model of transcription, which explicitly incorporates this interplay between TF copy number and its binding sites. We show that TF sharing enhances noise in mRNA distribution across an isogenic population of cells. Moreover, when a single gene copy shares its TFs with multiple competitor sites, the mRNA variance as a function of the mean remains unaltered by their presence. Hence, all the data for variance as a function of mean expression collapse onto a single master curve independent of the strength and number of competitor sites. However, this result does not hold true when the competition stems from multiple copies of the same gene. Therefore, although previous studies showed that the mean expression follows a universal master curve, our findings suggest that different scenarios of competition bear distinct signatures at the level of variance. Intriguingly, the introduction of competitor sites can transform a unimodal mRNA distribution into a multimodal distribution. These results demonstrate the impact of limited availability of TF resource on the regulation of noise in gene expression.

Marian Walhout appointed inaugural Maroun Semaan Chair in Biomedical Research

April 12, 2017

Marian Walhout, Ph.D.UMass Medical School will invest three faculty members into newly endowed chairs and three more to existing endowed chairs, according to a vote by the University of Massachusetts Board of Trustees at its April 12 meeting.

Marian Walhout, PhD, professor of molecular medicine and co-director of the Program in Systems Biology, has been appointed the inaugural recipient of The Maroun Semaan Chair in Biomedical Research. Dr. Walhout is a pioneer among those working to understand how genes are expressed on a system level, and how these complex biological networks adapt to various conditions. Her research, which combines large-scale data sets and uses computational modeling to unravel regulatory networks involved in metabolic and genetic development, has advanced the fundamental understanding of these systems and offers potentially new and innovative pathways to treat human disease.

Latest Publications


The Mitchell Lab

Assembling stable syntrophic Escherichia coli communities by comprehensively identifying beneficiaries of secreted goods


The Brewster Lab

Inherent regulatory asymmetry emanating from network architecture in a prevalent autoregulatory motif


The Dekker Lab 

Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics


The Dekker Lab 

Volume 53 Issue 5

Genetic and spatial organization of the unusual chromosomes of the dinoflagellate Symbiodinium microadriaticum


The Lee Lab

ELP-dependent expression of MCL1 promotes resistance to EGFR inhibition in triple-negative breast cancer cells

Although the activity of the epidermal growth factor receptor (EGFR) pathway is increased in triple-negative breast cancers (TNBC), patients are generally insensitive to EGFR inhibitors. Peter Cruz-Gordillo, Megan Honeywell, and colleagues found that this is because TNBC cells produced the prosurvival protein Mcl-1. A gene deletion screen revealed that insensitivity to the EGFR inhibitor erlotinib required MCL1 expression promoted by the ELP family of transcription-elongation regulators, particularly ELP4. The findings suggest that an ELP4–Mcl-1 mechanism masks erlotinib sensitivity in TNBC and that combining erlotinib with an Mcl-1 inhibitor might be effective in patients with TNBC.

Cruz-Gordillo P, Honeywell ME, Harper NW, Leete T, Lee MJ. (2020). ELP-dependent expression of MCL1 promotes resistance to EGFR inhibition in triple-negative breast cancer cells. Science Signaling 13(658), eabb982


Shank Lab

Expanding Molecular Coverage in Mass Spectrometry Imaging of Microbial Systems Using Metal-Assisted Laser Desorption/Ionization

A new study shows that transparent soil substitutes can be used to replicate the interactions of bacteria and fungi in soil, opening up a new approach to learning how soil microbes contribute to a healthy ecosystem. Elizabeth Shank, PhD, associate professor of microbiology & physiological systems and senior author on the study, describes how using two transparent soil substitutes allowed scientists to follow how soil bacteria rely on fungi to help them survive extended dry periods. 


Sharma K, Palatinszky M, Nikolov G, Berry D, Shank EA. (2020) Transparent soil microcosms for live-cell imaging and non-destructive stable isotope probing of soil microorganisms. Elife 9:e56275


Walhout Lab


WormPaths: Caenorhabditis elegans metabolic pathway annotation and visualization

Walker MD, Giese GE, Holdorf AD, Bhattacharya S, Diot C, García-González AP, Horowitz B, Lee Y, Leland T, Li X, Mirza Z, Na H, Nanda S, Ponomarova O, Zhang H, Zhang J, Yilmaz SL, Walhout AJM,. 2021 WormPaths: Caenorhabditis elegans metabolic pathway annotation and visualization, Genetics iyab089.


Youk Lab

Maire T, Allertz T, Betjes MA, Youk H. (2020) Dormancy-to-death transition in yeast spores occurs due to gradual loss of gene-expressing ability, Mol Syst Biol Mol Syst Biol 16:e9245.