Research

Our vision for 21st century science emerges from complementary strengths in drug discovery and development, preclinical imaging, proteomics, cell free synthesis, physiochemical analysis, and nanoscale imaging.

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Education

We educate, train, and inspire the next generation of transdisciplinary scientists to venture farther into the realm of unrealized research possibilities.

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Translation

We lower the barriers to discovery, and as a result, accelerate breakthroughs to solve the complexities of biology, and apply this new knowledge to improve the quality of life.

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Research

Our vision for 21st century science emerges from complementary strengths in drug discovery and development, preclinical imaging, proteomics, cell free synthesis, physiochemical analysis, and nanoscale imaging. The next waves of technology for early detection and treatment of a broad array of diseases will arise from this multi-pronged attack.

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Transforming Science. Transforming Life.

Chemistry of Life Processes Institute (CLP) researchers use the technologies of tomorrow to discover the diagnostic methods and therapies needed to save lives today. Chemists, engineers, and physicists team with life scientists and clinicians to change how we diagnose and treat cancer, cardiovascular and kidney disease, infectious diseases, neurodegenerative diseases, and trauma. Their efforts are built on extraordinary tools for discovery, analysis, and visualization developed and housed within a unique ecosystem designed to support the integration of expertise and methods across many scientific disciplines. This transdisciplinary convergence of knowledge is creating new fields of research that will have a long-lasting impact on human health and disease.

Transforming Science. Transforming Life.

Chemistry of Life Processes Institute (CLP) researchers use the technologies of tomorrow to discover the diagnostic methods and therapies needed to save lives today. Chemists, engineers, and physicists team with life scientists and clinicians to change how we diagnose and treat cancer, cardiovascular and kidney disease, infectious diseases, neurodegenerative diseases, and trauma. Their efforts are built on extraordinary tools for discovery, analysis, and visualization developed and housed within a unique ecosystem designed to support the integration of expertise and methods across many scientific disciplines. This transdisciplinary convergence of knowledge is creating new fields of research that will have a long-lasting impact on human health and disease.

Our Impact

In the Immune System’s Trenches, a New Discovery

Few everyday scenarios illicit as much trepidation as a nearby sneeze during flu season. Suddenly surrounded by tens of thousands of potentially virus-filled particles, a person’s evolving cellular reaction actually matters far more than the ability to shield one’s face.

“Most people know about the body’s immune system, but not as many understand that every cell has its own immune defenses,” says Curt Horvath, molecular biosciences, who studies the cellular recognition of and response to ribonucleic acid (RNA) viruses, as well as the manner in which viruses employ immune-evasion tactics. “The cell’s defense system acts as an initial barrier and is what prevents us from getting sick from every infectious particle we’re exposed to.”

Horvath and Northwestern graduate student Roli Mandhana recently published a pathbreaking study of RNA viruses in Scientific Reports, in which they identified hundreds of new such viruses induced by infection. RNAs are responsible for the signaling cascades  — the innate immune response — that result in widespread changes to gene expression when a virus is recognized as foreign. RNAs also carry out many biological functions that keep humans healthy, including the coding, decoding, regulation, and expression of genes.

Northwestern graduate student Roli Mandhana was first author of a pathbreaking study of RNA viruses recently that was published in Scientific Reports.

The most widely studied virus-inducible RNAs (viRNAs) encode proteins that mediate virus response; however, the completion of the Human Genome Project in 2003 and technological advances in genome-wide sequencing since have provided researchers with an opportunity to explore viral dynamics further.

“As we looked more closely, we found a lot of RNAs unable to encode proteins but whose levels change because of a response to infection,” says Horvath, a professor in the Weinberg College of Arts and Sciences. “As our lab and others identify more of these noncoding viRNAs, researchers are finding unexpected functions for them.”

The Horvath lab’s experiments most frequently involve infecting cell cultures with viruses and then monitoring the RNA response with the support of Northwestern’s NUSeq Core Facility, the High Throughput Analysis Laboratory within the Chemistry of Life Processes Institute (CLP), and the University’s Quest High Performance Computing Facility.

High throughput screening is a critical aspect of Horvath’s work because it greatly reduces the time it takes to scan large numbers of cell lines.

“We can now look at every gene in the cell simultaneously through these deep sequencing approaches,” he says. “At Northwestern, we are lucky to have the support of expert core facilities to enable us to easily pursue new and technologically advanced research directions. University investment in state-of-the-art support infrastructure pays dividends to every research area.”

Having identified the novel viRNAs — which the lab refers to as nviRNAs — Horvath set out to screen different viruses, including influenza A and herpes simplex virus 1. The goal was to cast a broad net and determine which nviRNAs were generalizable and which were virus specific.

The recent discoveries build upon prior research by former graduate student Jonathan Freaney, who investigated regulators of antiviral response and found widespread activity well beyond what researchers knew. The latest findings may someday help reveal why some viral infections — like HIV — are adept at evading immune response.

“We still don’t know what role these newly discovered noncoding RNAs play, but we now know that they exist and we can further explore if they are controlling the virus infection or helping the virus to replicate,” says Horvath. “Knowing those answers would introduce the possibility of targeting them for diagnostics or therapeutics.”

As a basic scientist, Horvath will rely on his lab’s latest discoveries to apply for new grants as he continues to help construct a more complete understanding of the total cellular response to virus infection.

“The ability to take these basic research findings and translate them into some diagnostic, therapeutic, or antiviral remedy really relies on our ability to take the next steps and connect our observation to some functional mechanistic consequence during the course of a virus infection,” he says. “We will continue to make these characterizations at the cellular level, but the long-term plan is to work with additional collaborators to explore what is happening in living models.”

By Roger Anderson

Curt Horvath is a member of the Chemistry of Life Processes Institute and faculty director of the Institute’s High Throughput Analysis Laboratory, an open resource for projects involving massively parallel experiments that open up unexpected frontiers in basic science and accelerate development of new medicines. Learn more about how the HTAL can advance your research.

Original story published by Northwestern Research on January 10, 2019.

Pediatric leukemia ‘super drug’ could be developed in the coming years

Northwestern Medicine scientists have discovered two successful therapies that slowed the progression of pediatric leukemia in mice, according to three studies published over the last two years in the journal Cell, and the final paper published Dec. 20 in Genes & Development.

When a key protein responsible for leukemia, MLL, is stabilized, it slows the progression of the leukemia, the most recent study found. The next step will be to combine the treatments from the past two years of research into a pediatric leukemia “super drug” to test on humans in a clinical trial.

The survival rate is only 30 percent for children diagnosed with MLL-translocation leukemia, a cancer that affects the blood and bone marrow. Patients with leukemia have a very low percentage of red blood cells, making them anemic, and have approximately 80 times more white blood cells than people without cancer.

“These white blood cells infiltrate many of the tissues and organs of the affected individuals and is a major cause of death in leukemia patients,” said senior author Ali Shilatifard, the Robert Francis Furchgott Professor of Biochemistry and Molecular Genetics and Pediatrics, the chairman of biochemistry and molecular genetics and the director of Northwestern’s Simpson Querrey Center for Epigenetics. “This is a monster cancer that we’ve been dealing with for many years in children.”

There are several types of leukemia. This research focused on the two most common found in infants through teenagers: acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL).

For the past 25 years, Shilatifard’s laboratory has been studying the molecular function of MLL within its complex known as COMPASS (Complex Proteins Associated with Set1). Most recently, it was demonstrated that COMPASS components are one of the most frequently identified mutations in cancer. The next step of this work will be to bring the drug to a clinical trial setting, which Shilatifard said he hopes will happen in the next three to five years.

“I’ve been working on this translocation for more than two decades, and we’re finally at the point where in five to 10 years, we can get a drug in kids that can be effective,” Shilatifard said. “If we can bring that survival rate up to 85 percent, that’s a major accomplishment.”

Earlier work from Shilatifard’s laboratory published in Cell in 2018 identified compounds that could slow cancer growth by interrupting a gene transcription process known as “Super Elongation Complex” (SEC). It was the first compound in its class to do this.

This MLL stabilization process discovered in the most recent paper could potentially work in cancers with solid tumors, such as breast or prostate cancer, said first author Zibo Zhao, a postdoctoral research fellow in Shilatifard’s lab.

“This opens up a new therapeutic approach not only for leukemia, which is so important for the many children who are diagnosed with this terrible cancer, but also for other types of cancers that plague the population,” Zhao said.

“The publication of these four papers and the possibility of a future human clinical trial could not have happened if it weren’t for the cross-disciplinary collaboration at Northwestern,” Shilatifard said.

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This collective research was made possible because of the interdisciplinary collaboration between Northwestern’s chemistry, biochemistry, biology and clinical departments, Shilatifard said.

Other Northwestern co-authors included Lu Wang, Andrew Volk, Noah Birch, Kristen Stoltz, Elizabeth Bartom, Stacy Marshall, Emily Rendleman, Carson Nestler, Joseph Shilati, Gary Schiltz and John Crispino. Shilatifard and Crispino are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Funding for this research was provided in part by the National Institutes of Health grant T32 CA070085 and the National Cancer Institute Outstanding Investigator Award R35-CA197569.

By Kristin Samuelson.

Original story appeared in Northwestern Now on December 21, 2019.

Ali Shilatifard is a member of the Chemistry of Life Processes Institute. Kirsten Stoltz and Gary Schiltz work in Chemistry of Life Processes Institute’s Center for Molecular Innovation and Drug Discovery. 

Click here to learn more about the resources and research capabilities of CMIDD.

Carla Rosenfeld appointed associate director of CLP’s Quantitative Bioelement Imaging Center

The Chemistry of Life Processes Institute (CLP) has appointed Dr. Carla Rosenfeld associate director, Quantitative Bioelement Imaging Center (QBIC) at Northwestern University.

In this capacity, Rosenfeld will lead the facility into its next phase of growth and development as a national resource for bio-element imaging and analysis.  Her responsibilities include operation and routine maintenance of facility instruments, training and supervising student users, supervision of technical staff, grant writing and advising faculty on experimental design and data analyses.

Previously, Rosenfeld held the position of visiting research associate in the Molecular Environmental Sciences Group, Biosciences Division, Argonne National Laboratory, where she focused on trace metal biogeochemistry and water quality. Rosenfeld completed her postdoctoral fellowship in environmental chemistry and microbiology at the Smithsonian Institution (Department of Mineral Sciences) and University of Minnesota (Department of Earth Sciences), where she held an NSF Postdoctoral Fellowship. She received her Ph.D. research in Soil Science and Biogeochemistry from Penn State University and B.S. degree in Chemistry from McGill University.

Rosenfeld’s expertise includes analysis of metals in numerous environmental and biological matrices and preparing solid samples for analysis and other analytical approaches including electron microscopy, chromatography, Fourier transform infrared (FTIR) spectroscopy, X-ray absorption spectroscopy (XAS), and X-ray diffraction (XRD), and X-ray fluorescence (XRF).  An experienced manager and grant writer, she has also overseen multiple interdisciplinary environmental science projects, operated and maintained numerous analytical instruments, coordinated field and laboratory endeavors and trained and supervised students.

About QBIC

Located in Silverman Hall on Northwestern University’s Evanston campus, QBIC focuses on the development and application of novel tools, methods, and instrumentation for the analysis and mapping of inorganic elements in biological samples.  Transitional metal atoms are found within all living cells and are conserved during evolutionary processes. Through a suite of high-resolution instruments capable of quantitatively imaging biologically essential elements in individual cells, QBIC’s instrumentation enables physical, life, and material scientists to analyze metal quotas at scales ranging from the subcellular level to entire ecosystems shaping global biogeochemical cycles. This work sheds light on the co-evolution of microbial and eukaryotic life within a broad range of challenging chemical environments.

A shared resource facility serving investigators within the Northwestern scientific community and beyond, QBIC provides researchers with access to state-of-the-art imaging and quantification instrumentation while supporting its use with an expert technical staff that offers a range of services, including instrument training, sample preparation and analysis, experiment design, and grant proposal assistance.  The combination of both extremely high sensitivity elemental analysis and high resolution imaging enables QBIC customers to perform cutting edge experiments with expert staff support. Operating under the direction of Thomas O’Halloran, Charles E. and Emma H. Morrison Professor of Chemistry and founding director of CLP, QBIC is the only facility in the greater Chicago area with multiple inductively coupled plasma (ICP) systems dedicated to the analysis of inorganic elements in biological and materials samples. Additionally, QBIC offers the only laser ablation system dedicated to mapping biological samples in the Chicago area.

by Lisa La Vallee

Full-Body Scan Could Improve Chemotherapy Effectiveness

A new full-body scan could help clinicians to better assess toxicity during cancer treatment, according to a Northwestern Medicine study published in Clinical Cancer Research.

The scan, which detects the presence of molecules exposed during tissue damage, could give a precise evaluation of patient toxicity during chemotherapy, said Ming Zhao, PhD, associate professor of Medicine in the Division of Cardiology and senior author of the study.

“After a single chemotherapy treatment, you already see changes,” said Zhao, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “This could give doctors the opportunity to intervene and reduce the dose or switch to another drug for example, hopefully preventing any further damage to the patient.”

SPECT/CT fusion images of the femurs in control and methotrexate treated animals are presented. Significant signal elevation was detected in the bones. Hematoxylin and eosin-stained section of femoral bone demonstrates a depletion of hematopoietic cells in bone marrow of methotrexate-treated animals.

Steven Johnson, ’18 PhD, postdoctoral fellow in the Zhao laboratory, was lead author of the study.

Chemotherapy works by targeting and killing actively dividing cells. While this fights cancer, casting such a wide therapeutic net damages healthy cells as well, resulting in potentially harmful side effects in patients.

While there are a range of clinical tools to measure cancer’s response to chemotherapy, tools that assess patient toxicity are limited, according to Zhao.

“While tumor kill is the main therapeutic goal in anticancer treatment, toxicity is equally important because it tends to dictate the patients’ tolerance ceiling for treatment,” Zhao said. “Current tools rely on patient symptoms and subsequent blood or serum tests, which can lag behind actual tissue damage. Instead, an imaging based method could be a quicker and more accurate way to ascertain patient toxicity.”

In the current study, scientists mapped tissue damage in rodent models using a novel whole-body imaging technique developed in collaboration with the Chemistry of Life Processes Institute’s Center for Advanced Molecular Imaging (CAMI). The technique detected a lipid molecule that is not accessible in normal cells, but becomes visible in dead and dying cells.

The lipid molecule, called phosphatidylethanolamine (PE), usually resides inside the cell. However, when a cell dies, it deactivates enzymes that maintain the asymmetrical structure of the cell membrane, redistributing PE to the cell surface.

“This provides a molecular marker for detecting cell death,” Zhao said.

The scientists compared the results of blood and serum tests to the imaging results, finding the signal changes in the scans correlated with the results of the conventional tests — with the scan providing earlier, broader and more dynamic information, according to Zhao.

“Damage to the skin can be highly local; if you take a biopsy, you might miss it,” he said. “With this test, you look at the entire organ; if there is a heterogeneous distribution of damaged tissue, you can tell where it went wrong.”

They also tested the scan in both male and female rodents, finding it detected damage in reproductive organs, a life-changing issue for some patients.

“Reproduction is a major issue in younger patients,” Zhao said. “This may help predict if this individual will have problems down the line.”

Further, the scan could also detect damage, or lack thereof, in the tumor itself, providing another data point to drive clinical decision making.

“A lack of PE on the tumor will tell you that the drug isn’t killing the tumor effectively, suggesting you should make the decision to switch to another treatment,” Zhao said. “This scan should help optimize cancer treatment to maximize tumor damage and minimize side effects.”

Now, Zhao and his collaborators are exploring the technology’s potential in humans.

“We’ve shown the proof of concept; this can be done,” Zhao said. “But for human translation, we need to make sure everything works well — and safely.”

Currently, the scientists are working on implementing a second-generation imaging agent, which could produce significantly greater data quality for clinical translation.

The study was an inter-departmental and interdisciplinary effort, involving authors from different areas of expertise. Co-authors included Chad Haney, PhD, research associate professor of Chemistry of Life Processes Institute, Biomedical Engineering, and of Radiology; Gennadiy Bondarenko, PhD, postdoctoral fellow; Emily Waters, research associate at the CAMI; Andy Tran, research assistant; Thomas O’Halloran, PhD, professor of Medicine in the Division of Endocrinology, Metabolism and Molecular Medicine. Former Feinberg faculty Raymond Bergan, MD; Andrew Mazar, PhD; Andrey Ugolkov, MD, PhD and Lin Li, MD, were also co-authors.

This work was funded by a “Provocative Questions” grant from the National Cancer Institute (NCI) R01 CA185214 awarded through the Chemistry of Life Processes Institute, 1S10OD016398 to fund acquisition of the SPECT/CT scanner in CAMI, and 5R01HL102085 and NCI CCSG P30

by Will Doss

Original story published in Northwestern Medicine on January 9.

Research Forum

Jasper Dittmar & Ashley Ives
February 4th

CMIDD Seminar

David Nagib, PhD
Assistant Professor of Chemistry
Ohio State University
February 27th

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CMIDD Seminar

Thomas Snaddon, PhD
Assistant Professor of Chemistry
Indiana University
March 12th

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Seminar

Dennis Dougherty
California Institute of Technology
April 1st

The Institute manages eight shared research facilities. These facilities represent a $25M investment in high‐end instrumentation and expertise and provide 50 new services that enable investigators to identify, design and refine potential new therapeutics and diagnostics and to visualize their activity in living cells and tissues. The cores’ PhD level personnel develop powerful new tools and methods to support new basic and translational research at Northwestern and across the Midwest.

Biological Imaging Facility

Photonic and electron instruments, allowing researchers to capture high-quality images and videos of their specimens.

Center for Advanced Molecular Imaging

Imaging resources span length scales of molecules to whole animals. Instruments include MRI, IVIS Spectrum, SPECT, and PET.

ChemCore

Medicinal and synthetic chemistry, molecular modeling and compound purification services.

Developmental Therapeutics Core

Operational laboratory that supports translational projects and exploratory drug development work.

High Throughput Analysis Laboratory

Instrumentation and expertise for the development and execution of high throughput biological analysis and screening.

Proteomics Core

Instrumentation and expertise to analyze proteins using mass spectrometry. Specializing in intact protein analysis.

Quantitative Bio-element Imaging Center

Quantitation and localization of bioelements using ICP mass spec, customized Hitachi HD2300 STEM for cryo-bio EM, and atomic absorption mass spectometry.

Recombinant Protein Production Core

Expression and purification of recombinant or synthetic biologics and cultivation of microbial, insect, and mammalian cells.