Scientists across disciplines, departments and schools at Northwestern University are teaming up to accelerate Northwestern Medicine research and bring innovative ideas to fruition. Faculty from chemistry, engineering, communications and more are working to tackle unanswered questions in healthcare and medicine.
“The most intractable problems in medicine today require inquisitive minds that can approach a situation from a different set of perspectives, providing more specificity and precision,” says Eric G. Neilson, MD, vice president for Medical Affairs and Lewis Landsberg Dean. “When we tap into the rich pool of expertise that exists in the University’s various schools, we can develop the most creative and well-rounded solutions.”
Here we share a number of projects in which Northwestern faculty across myriad fields are working together to advance the progress of patient care, treatments and outcomes.
The Interface between Materials & Biology
Combining disciplines in biology, chemistry and engineering, synthetic biologists at Northwestern are working to make non-biological materials for industrial and medical purposes.
“Cells have an amazing ability to make interesting and complex things,” says Milan Mrksich, PhD, professor of cell and molecular biology and professor of biomedical engineering and chemistry at the McCormick School of Engineering and Applied Sciences, Feinberg School of Medicine, and Weinberg College of Arts & Sciences. “We can take an organism, a microbe, plant or cell and genetically reprogram it to make a molecule or protein that is useful.”
Mrksich has developed a novel assay that can evaluate tens of thousands of enzyme reactions in cells within a day or two. This method helps define reaction conditions and identify the components needed to produce the highest yield of molecules and speed up the process for finding effective drug therapies.
Mrksich’s colleague, Michael Jewett, PhD, assistant professor of chemical and biological engineering at McCormick, works to develop and optimize cell-free systems to create new therapies. A cell-free system avoids the need to balance a cell’s life processes, such as importing nutrients and exporting wastes, and the production of the molecule of interest.
“This is a really powerful approach and Northwestern is the intellectual home for developing these methods,” Mrksich says.
Merging Physical Sciences & Oncology
Northwestern University received a five-year, $9.6 million grant from the National Cancer Institute as part of a new center, the Chicago Region Physical Science-Oncology Center (CR-PSOC), that unites physical scientists and cancer researchers from Northwestern, the University of Chicago, and University of Illinois at Chicago to solve problems in cancer.
Thomas V. O’Halloran, PhD, Charles E. and Emma H. Morrison Professor in Chemistry at Weinberg, and Jonathan D. Licht, MD, former chief of medicine-hematology/oncology at Feinberg, will lead the CR-PSOC and together the team will study changes in the epigenome and the metallome, the metal ion content of the cell, which support cancer development.
Specifically, CR-PSOC investigators will use physical science approaches and novel imaging methods to determine whether changes in chromatin folding result in aberrant patterns of gene expression that drive cancer progression. The scientists will translate these advances into a deeper understanding of cancer biology and into therapies.
Applying Nanotechnology to Medicine
For 10 years, the National Cancer Institute has funded collaborative work between scientists at the Robert H. Lurie Cancer Center of Northwestern University and the International Institute for Nanotechnology at Northwestern to explore how nanotechnology can improve cancer diagnosis and treatment.
Led by Chad Mirkin, PhD, professor of medicine at Feinberg and chemistry at Weinberg, and Leonidas Platanias, MD, PhD, director of the Lurie Cancer Center, the Northwestern University Center of Cancer Nanotechnology Excellence (NU-CCNE) joins clinicians, cancer biologists, engineers and clinicians.
“This is a very translational, extremely critical area of biomedical research,” says Dr. Platanias. “Important discoveries happen when you bring people from different fields together for a common goal.”
For example, in one recently published study supported by the NU-CCNE, scientists conjugated gold nanoparticles with a small RNA molecule to suppress cancer-causing genes in mice with glioblastoma mulitforme (GBM), a deadly and incurable type of brain tumor.
In a third phase of funding beginning this fall, the NU-CCNE will focus on three major projects, in addition to pilot projects with junior faculty:
- Design Rules for Spherical Nucleic Acids that Target Cancer: Milan Mrksich and Mary Hendrix, PhD, president and scientific director of the Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago
- Spherical Nucleic Acids for Metabolic Reprogramming of Malignant Glioma: Alexander Stegh, PhD, assistant professor of neurology and medicine, and C. David James, PhD, professor of neurological surgery and biochemistry and molecular genetics, both at Feinberg
- Spherical Nucleic Acids as Immunotherapeutic Agents for Prostate Cancer: Chad Mirkin and Bin Zhang, MD, PhD, associate professor of medicine-hematology/oncology and microbiology-immunology at Feinberg.
In addition to using nanotechnology to create therapies for cancer, Melina R. Kibbe, MD, professor of surgery-vascular at Feinberg, and Samuel I. Stupp, PhD, director of the Louis A. Simpson and Kimberly K. Querrey Institute for BioNanotechnology in Medicine (SQI), are working together to develop nano- and microscale therapies to prevent restenosis, the recurrence of blood vessel narrowing.
“Our technology would benefit patients undergoing any vascular intervention, including balloon angioplasty, stenting, or bypass grafting,” explains Dr. Kibbe.
“Because these highly designed therapies can be targeted to multiple different cell types, our research can have a broader impact on the fields of preventive cardiology, cancer and rheumatology, among other diseases. Since no similar therapy currently exists in the clinical arena, our smart technology would be paradigm-shifting.”
Global Fight against Hepatitis C
Hepatocellular carcinoma (HCC), a highly lethal cancer with more than 80 percent of cases occurring in the developing world, is typically caused by chronic viral infections including hepatitis C. Robert Murphy, MD, director of the Center for Global Health, Kara Palamountain, MBA, research assistant professor at Kellogg School of Management, Sally McFall, PhD, research associate professor of biomedical engineering at McCormick, and Robert Elghanian, PhD, research assistant professor of biomedical engineering at McCormick, are developing diagnostic tests to detect and monitor chronic hepatitis C infections for use in low- and middle-income countries. They hope that earlier diagnosis will reduce HCC mortality.
Partnering to Halt Neurodegenerative Diseases
There is an enormous need for a therapeutic strategy for slowing or stopping Parkinson’s disease (PD) progression, the second most common neurodegenerative disease. Preclinical studies in the lab of D. James Surmeier, PhD, chair of the Department of Physiology at Feinberg, implicated a relatively rare type of calcium channel in the disease. This research has been supported by epidemiological studies, leading to a National Institutes of Health-sponsored, $23 million clinical trial in North America, directed by Tanya Simuni, MD, professor of neurology, to determine if the FDA-approved calcium channel antagonist isradipine can slow disease progression. One potential problem with isradipine is its lack of selectivity. Surmeier and Richard Silverman, PhD, professor of chemistry at Weinberg, have teamed up to develop a next-generation drug that overcomes this shortcoming.
In addition, over the past decade, Sam Stupp’s laboratory has focused on using nanostructures to create bioactive biomaterials that mimic the architecture of natural extracellular matrices for use in regenerative medicine; targets include the regeneration of musculoskeletal tissues as well as brain tissue, spinal cord and peripheral nerves.
To apply this knowledge to neurodegenerative disorders such as Parkinson’s disease, Stupp, professor in the McCormick School of Engineering, is working with Dimitri Krainc, MD, chair of the Department of Neurology, to study the effect of a nanofiber gel on human dopaminergic neurons (neurons in the midbrain that are the main source of dopamine, the chemical messenger that controls muscle movement).
They took induced pluripotent stem cells (iPS) from patients with genetic and sporadic Parkinson’s disease, differentiated the iPS cells into dopaminergic neurons and encapsulated them in the nanofiber gel. The team has seen some promising in vitro results that indicate this material could be used to improve the survival and formation of neuronal networks of iPS-derived dopaminergic neurons. The ultimate goal is to develop it into a therapy for patients.
Reproductive Biology Brings Scientists Together Across Fields
Interdisciplinary projects in the Center for Reproductive Studies work to advance reproductive biology with the help of investigators in bioengineering, chemistry and medicine. By understanding the biology of reproduction, scientists can develop future medical treatments for infertility, pregnancy-related disorders, diseases of the reproductive tract and gynecological cancers.
Kelly Mayo, PhD, director of the Center for Reproductive Science at McCormick, studies the molecular mechanisms regulating normal reproductive function, with relevance to reproductive disorders that impact fertility. His team has used imaging technologies on mouse genetic models to visualize cell-signaling systems in ovaries to gain insights about different cell types in the developing follicle.
The laboratories of Thomas O’Halloran, PhD, director of the Chemistry of Life Processes Institute at Weinberg, and Teresa Woodruff, PhD, director of the Women’s Health Research Institute at Northwestern University, collaborate to find the roles of zinc fluxes in oocyte maturation and egg fertilization using newly synthesized chemical probes. Their recent study shows there are thousands of zinc-loaded vesicles in the oocyte that serve as the source of the zinc sparks that are released from the egg upon fertilization. Their work will potentially help infertile couples have a healthy pregnancy.
Engaging College Freshmen in Health Behavior Changes
Bonnie Spring, PhD, director of Northwestern’s Center for Behavior and Health, professor of preventive medicine and at Weinberg, is launching a project this fall to prevent college students’ health loss.
The NUYou project will enroll 500 incoming Northwestern freshmen, who will use specially designed smartphone applications, social media and incentives to maintain or improve positive health behaviors. Students will be assessed annually to evaluate the effectiveness the NUYou intervention.
Spring, along with Northwestern students, computer scientists and Daniel Shor, PhD, clinical director of Counseling and Psychological Services in the Division of Student Affairs at Northwestern, used rapid iterative design processes to optimize the technologies. The result is a suite of interventions that will allow students to manage their time, receive relevant and timely health recommendations, connect with each other for support via social media, and challenge one another to create a health culture at Northwestern.
Social Science Plays Crucial Role in Research
“I’m a social scientist and not a clinician, so collaborations with Feinberg are essential to do my work,” he says.
For the past four years, Lambert has joined forces with Michael Wolf, PhD, ’02 MPH, professor of medicine-general internal medicine and geriatrics, Center for Healthcare Studies and medical social sciences, to design and implement a health literacy intervention for patients with type II diabetes. Currently in trials at a University of Illinois at Chicago clinic, the intervention consists of patients getting redesigned information before, during and after they receive medications. The goal is to help patients take their medication more safely and effectively.
Lambert also works with Howard Kim, MD, an instructor in the Department of Emergency Medicine, to study the prescribing frequency of opioids and benzodiazepines, since both medications slow breathing and when taken together can suppress respiration or impair a person’s reflex to breathe. After they collect preliminary data, the team will design an intervention to discourage physicians from prescribing these drugs together.
In an effort to better understand HIV, Brian Mustanski, PhD, associate professor in the Department of Medical Social Sciences and director of the IMPACT LGBT Health Program, is working on a study called RADAR that brings together experts in virology, genetics, social science and public health to understand biological, individual, relational, network and community-level drivers of the disease.
Mustanski is working with Noshir Contractor, PhD, director of the Science of Networks in Communities Research Group at Northwestern University, and Michelle Birkett, PhD, research assistant professor of medical social sciences. The team will longitudinally measure the social, sexual and drug networks of young men who have sex with men (YMSM) and analyze how these networks may be driving HIV. They have already produced a new software program that allows for the user-friendly collection of network data.
Other RADAR projects include characterizing the developmental trajectories of HIV risk and substance use, as well as conducting innovative analyses examining the influences of romantic partners on the participants’ health behaviors, led by Dan Mroczek, PhD, professor of psychology at Weinberg and medical social sciences at Feinberg, and Michael Newcomb, PhD, assistant professor of medical social sciences.
Fostering Translational Research between Basic Scientists and Clinicians
In 2015, the Robert H. Lurie Cancer Center at Northwestern University launched its first Translational Bridge Program, an award to propel basic science research into clinical trials. Postdoctoral fellows design and execute projects targeting specific cancer types under the mentorship of a laboratory investigator and a clinician.
The first four projects include:
- Ovarian Cancer: Vadim Backman, PhD, professor of biomedical engineering at McCormick, Shohreh Shahabi, MD, professor of obstetrics and gynecology-gynecologic oncology at Feinberg, and postdoctoral fellow Lusik Cherkezyan, PhD, will use a biophotonics technology invented in the Backman lab, called Partial Wave Spectroscopic microscopy, or nanocytology, which enables the sensing of genetic/epigenetic changes in cells at the nanoscale, to diagnose ovarian cancer at an earlier stage.
- Breast Cancer: David R. Gius, MD, PhD, professor of radiation oncology and pharmacology at Feinberg, and Cesar Santa-Maria, MD, assistant professor of medicine-hematology/oncology at the Lurie Cancer Center, are working to better understand the relationship between the SIRT3 gene and luminal B breast cancer. They suggest that reactive oxygen species and SIRT3 could potentially be used in identifying new therapeutics.
- Brain Cancer: Jeffrey Raizer, MD, professor of neurology at Feinberg, partnered with Thomas V. O’Halloran, PhD, and Elden Swindell, PhD, postdoctoral fellow, to elucidate the anti-tumor activity of a targeted nano-liposomal delivery vehicle (“nanobins”) loaded with arsenic trioxide in a brain tumor (glioma) mouse model. They can use the information gathered about the kinetics of drug delivery to gain a deeper insight into how these nanobins may be used in glioma treatment.
- Lymphoma: Ali Shilatifard, PhD, chair of the Department of Biochemistry and Molecular Genetics at Feinberg, has teamed up with Jane Winter, MD, professor of medicine-hematology/oncology, and Amir Behdad, MD, assistant professor of pathology, to study how mutations in the expression of the protein MLL4 lead to lymphomas. They will test antibodies developed by Shilatifard’s lab on human lymphomas and observe MLL4 expression.
Improving Healthcare Systems through Engineering
Research projects from Feinberg’s Center for Engineering and Health are building tools to improve health care delivery. Sanjay Mehrotra, PhD, the center’s director and professor of industrial engineering and management at McCormick, said that they are partnering with clinicians, health scientists, engineers and mathematicians to create safer medical care.
Mehrotra and his team created a prototype of a “smart” pill bottle. When triggered, the camera-based technology takes a picture of the bottle and its contents. The team will test the technology with HIV patients to manage their medication regimen. Participants include David Mohr, PhD, director for the Center for Behavioral Intervention Technologies at Feinberg, C. Hendricks Brown, PhD, director of the Center for Prevention Implementation Methodology at Feinberg, and Richard D’Aquila, MD, director of the Northwestern HIV Translational Research Center.