Illinois Institute Of Technology

NSF Awards · FY 2024 · 2024-07

Network testbeds provide shared platforms for researchers to carry out a wide range of network experiments. These platforms are constantly being reconfigured as researchers temporarily lease resources for their experiments. These resources increasingly involve programmable network hardware and software -- such as smart network interfaces and programmable soft switches -- that are used by researchers to develop new ideas. Moreover, programmable networking can also support the reconfiguration of testbed infrastructure itself to provide both flexibility and high performance. But this diffuse programmability introduces new challenges for observability of the network's state -- both from the perspective of the network operators and that of its users. This project will develop a new type of research instrument for observing the rapid and diffused state changes that are possible in programmable networks. This project brings together investigators from Illinois Institute of Technology, SRI International, and Georgetown University, to apply three concepts to network testbeds: (1) Remote Data Plane Attestation: Develop evidence generation, provenance capture, and program state attestation capabilities for a P4 programmable network device as well as "tuning parameters" to enable researchers and testbed operators to trade-off integrity assurance with computational overhead, (2) Programmable Network Provenance: Provide testbed users (network researchers and testbed operators) trustworthy information about past network configurations to establish ground truth, perform troubleshooting, and root-cause analysis of aberrant network behavior, and (3) User-Centric Network Views and Analytics: Provide testbed users with the capability of filters and faceted queries that provide trustworthy views of network equipment state and paths taken by network flows. This project will produce the following societal advancements: (1) improve the trustworthiness and reproducibility of scientific results discovered on programmable network testbeds, (2) contribute to open-source software tools for attested network provenance, (3) build new connections between members of the project team with the FABRIC testbed research community, and (4) educate undergraduate and graduate students through coursework and internships. The materials developed in this project -- including code, documentation, and papers -- will be made available at http://crease.cs.iit.edu This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2026 · 2024-04

Ex vivo intraoperative surgical basal margin analysis in head and neck cancer resection: clinical validation In a clinical collaboration with the University Medical Center Groningen (UMCG), Netherlands—led by Oral and Maxillofacial Surgeon, Dr. Witjes—we will advance and clinically test an intraoperative dual-aperture fluorescence ratio (dAFR) imaging system and an automated data analysis (ADA) approach that can analyze an entire resected-tissue basal margin in <1 min for head and neck squamous cell cancer (HNSCC) resection surgery. This is a significant improvement upon currently used frozen-section histopathology that requires >30 min and can only be done for a limited number of resected-tissue locations. The project will specifically focus on improving detection and localization of inadequate (positive and close) basal surgical margins, critical for patient survival. Over 3 million individuals across the globe are diagnosed with head and neck squamous cell carcinoma (HNSCC) each year. At present, surgical intervention is the primary treatment; however, owing to the complexity of the anatomy in the head and neck, >20% of procedures may fail to attain tumor-free surgical basal margins (defined as greater than 5 mm of healthy tissue surrounding the deep edge of the resected tumor). Unfortunately, because of slow resected-tissue processing, patients are often sent home before margins are fully assessed. While some patients can return for re-resection, for many, health concerns or substantial post-resection reconstruction surgeries make re-resection infeasible, and radiotherapy and/or chemoradiotherapy is needed. Patients with inadequate margins have <15% chance of surviving for 5 years post-surgery, compared to a >80% chance of survival for patients with free margins and no metastatic disease. Before dAFR imaging and surgery, patients are injected with a fluorescent epidermal growth factor receptor (EGFR)-targeted antibody, and intraoperative dAFR images of resected basal margins are taken and analyzed. Our preliminary results from a proof-of-concept dAFR imaging system indicate almost perfect detection rate of inadequate as well as clear margins. In this project, we propose necessary imaging system upgrades and to develop an automated data analysis to remove the need for clinical expert manual segmentation of images. The proposed approach will be validated and tested against state-of-the-art surgical guidance methods in an 80-patient clinical study at UMCG, in terms of detection and localization of inadequate basal margins through ROC and LROC assessments.

NIH Research Projects · FY 2026 · 2023-12

Cardiomyopathies are a significant cause of death and morbidity with limited treatment options. A substantial fraction (30-60%) of these cardiomyopathies has been identified as “diseases of the sarcomere” having their origin in point mutations in sarcomeric proteins leading to dysregulation of acto- myosin interactions with consequent functional deficits. Current therapies are mostly not disease specific and focus on symptoms rather than on mitigating the root causes in sarcomere dysregulation. Muscle contractility is governed by both the classic and extensively studied Ca2+-mediated thin filament- based regulatory mechanism and newly discovered, but very poorly understood, thick filament based regulatory mechanisms. In this proposal, our over-arching hypothesis is that thick filament regulatory mechanisms are critical modulators of muscle function. Improved understanding of these mechanisms will identify novel drug targets, and the desired characteristics of therapeutic compounds, that are necessary to mitigate the structural and functional defects underlying myocardial pathophysiology. We have demonstrated that porcine myocardium, the closest model system for human hearts, is an excellent experimental system for our proposed structural and functional driven studies, with the expected findings readily extrapolatable to humans. We propose to investigate the structural, biochemical, and mechanical aspects of thick filament regulation mechanisms from porcine myocardium. Specifically, in Aim 1, we will decouple classical Ca2+ dependent thin filament-based regulation from the newly discovered Ca2+ dependent thick filament-based regulation mechanism by exchanging the native troponin complex with exogenous D65A troponin complex that abolishes Ca2+ binding capability to reveal the details of molecular mechanism and the physiological significance of this mechanism. In Aim 2, we will evaluate thick filament backbone stiffness from both actively contracted and passively stretched porcine myocardium to investigate the underlying mechanisms of myofilament length dependent activation. In Aim 3, we will interrogate the structural, biochemical and mechanical consequences of porcine myocardium in response to PKA treatment. Finally, in Aim 4, we will extend the new findings regarding thick filament regulatory pathways in healthy porcine myocardium to the pathological basis of thick filament dysregulation in hypertrophic, dilated and restrictive cardiomyopathies (HCM, DCM and RCM respectively) model porcine hearts. Results are expected to have immediate translational relevance by identifying potential therapeutic targets for sarcomere-based cardiomyopathies.

NIH Research Projects · FY 2025 · 2022-09

The objective of this proposal is to develop a prototype for the next generation multivariable automated insulin delivery (mvAID) systems (also called artificial pancreas) by integrating systems engineering and artificial intelligence (Al) techniques that will mitigate the effects of meals, physical activities ,acute psychological stress inducements and sleep irregularities without manual inputs by the user to tightly regulate the glucose levels of people with diabetes. The first generation of automated insulin delivery (AID) systems relied on hybrid closed-loop technology, collecting data from continuous glucose monitoring devices and requiring manual user inputs for mitigating the effects of meals and exercise. The multivariable AID that we developed provides a well-integrated next-generation system that analyzes historical and realtime data from different sources, including continuous glucose monitoring systems, insulin pumps, and wearable sensors in wristband physical activity trackers, to mitigate the effects of meals, physical activities, and acute psychological stress without manual inputs by the user. Meals, planned exercises, many physical activities of daily living, acute psychological stress, and sleep irregularities affect blood glucose levels differentially, challenging people with Type 1 diabetes to continuously consider all these complex factors in maintaining their blood glucose levels in the target range. Further improvement in glucose regulation can be achieved by developing novel, interpretable, and interactive Al techniques that can explain their predictions to medical care providers and AID users, and by integrating these Al techniques with systems engineering techniques to develop an Al-mvAID system. The function of these Al techniques is to predict the state of a person based on historical trends and current data, and provide additional valuable information to the mvAID system to relieve the users from onerous repetitive tasks for interpreting their current metabolic state, predicting the impact of their current actions on future variations in glucose levels, and tuning the parameters of the Al-mvAID controller. The goal is to produce a powerful userfriendly technology that integrates novel Al techniques with mvAID systems for minimal user burden in achieving tight control of glucose levels despite the many complex glycemic disturbances occurring in freeliving conditions, such as meals, physical activities, acute psychological stress, and sleep irregularities.

NIH Research Projects · FY 2025 · 2022-08

The applicant seeks this K99/R00 award to achieve research independence in intervention science, with a focus on using community-based participatory research (CBPR) principles to reduce the negative psychological and behavioral sequela that result from stigma. Transgender (trans) women are at high risk for HIV and substance misuse due in part to elevations in three interrelated areas underpinned by stigma: internalized stigma, psychological distress, and healthcare avoidance. Acceptance and Commitment Therapy (ACT) improves internalized stigma, psychological distress, and treatment engagement and may thereby reduce substance misuse and HIV risk. However, the effects of a gender affirming ACT intervention on internalized stigma, psychological distress, healthcare avoidance, and subsequent substance misuse and HIV risk among trans women are unknown. Peer-led interventions are essential to decrease trans women’s sense of isolation, share skills for coping with daily sources of stigma, and encourage pride in one’s gender identity. ACT is a promising evidence-based intervention for peer delivery as ACT has been effectively delivered by non-therapists before. The applicant thus proposes to adapt ACT to create a gender-affirming wellness intervention (ACT+GA) that targets substance misuse and HIV risk among trans women (K99 phase), conduct an open pilot trial of ACT+GA (K99 phase), and then run a rigorous test of its effectiveness, acceptability, appropriateness, and feasibility (R00 phase). During the K99 phase, she will collaborate with her mentorship team and the assembled community- advisory board to develop the ACT+GA manual based on focus group (k = 4-6, n = 4-6 trans women/group) and stakeholder feedback (n = 10-15 treatment providers, organizational leaders, and peer staff), and then address any necessary refinements identified during open pilot testing (n = 10 trans women). During the R00 phase, trans women will be randomly assigned to ACT+GA (n = 62) or treatment-as-usual (n = 62). Internalized stigma, psychological distress, healthcare avoidance, substance use, and HIV risk will be assessed at baseline, post- intervention, and at three and six-month follow-up. The coordinated training plan will allow the applicant to build on her strong foundation in CBPR and scholarship of HIV disparities in sexual and gender minoritized (SGM) populations, developing new skills in three areas critical to her independence: (1) adaptation of ACT for telehealth delivery by trans women, (2) early phase behavioral intervention development and testing, (3) depth of learning and application of qualitative and longitudinal quantitative methods. During the K99 Phase, her mentorship team will draw on its sustained track record in mentoring junior scholars to full independence. This will be accomplished through regular meetings, directed readings, hands-on tutorials, and support of her activity in workshops, seminars, and conferences. Completion of the R00 phase will generate data to support a future R01 application to test the effectiveness and implementation of ACT+GA on a larger scale. The K99/R00 award will thus provide the applicant with a platform to launch her independent career in transgender health and intervention science.

NIH Research Projects · FY 2025 · 2022-06

Synchrotron small angle X-ray fiber diffraction is the method of choice for obtaining structural and physiological information in the same experiment from active muscle. Experimental questions addressed range from basic biophysical questions regarding mechanisms of force production and regulation to increasingly pre-clinical questions relating structure to functional phenotype in animal models for cardiomyopathies and skeletal muscle disease as well as human muscle biopsies. Critical barriers to progress, however, has been the lack of robust, user-friendly tools for data reduction and computational tools for modeling diffraction patterns that can be used as an aid to interpret the data. In Aim 1 we propose to further develop the MuscleX software package as a highly automated data-reduction suite for small-angle fiber diffraction patterns from striated muscle. We will use artificial intelligence (AI) approaches to greatly increase efficiency, reduce influence of operator bias and improve reproducibility. New functionality will include global diffuse background subtraction using “deep learning”, the ability to analyze multiple superimposed diffraction patterns, autoindexing and automatic integration of diffraction peaks and unsampled layer lines. Robustness and reproducibility of code will be improved with rigorous testing and validation procedures. In Aim 2 we propose to develop a new tool, MUSICO-X for predicting two-dimensional X-ray diffraction patterns from striated muscle. MUSICO-X will be a new extension module for the multi-scale simulation package MUSICO that predicts small-angle X-ray fiber diffraction patterns simultaneously with the physiological data as a novel “forward problem” approach to extracting maximal information from static and dynamic time resolved X-ray fiber diffraction experiments on striated muscle. This new module will assign electron densities to components of the sarcomere using predicted molecular positions from MUSICO to predict simulated diffraction patterns that are tested and refined against representative X-ray diffraction and physiological data sets. These proposed software developments are broadly applicable to all muscle systems without a specific disease focus, and would not be fundable through usual mechanisms at NIAMS or HLBI. The availability of robust, user friendly data reduction code will increase the efficiency and reproducibility data from muscle fiber diffraction experiments on muscle. The proposed new simulation tool, encompassing both the structure and function of muscle, will provide a potent hypothesis generation and testing tool that can greatly increase the value of past, present, and future X-ray diffraction experiments on muscle.

NIH Research Projects · FY 2025 · 2021-12

PROJECT SUMMARY The sodium-dependent NADH: ubiquinone oxidoreductase (Na+-NQR) is the main ion transporter in hundreds of pathogenic bacteria, including Vibrio cholerae, the causal agent of cholera, a devastating gastrointestinal disease with a worldwide distribution that has developed multidrug-resistant phenotypes. Na+- NQR fulfills two essential roles in V. cholerae cell physiology, as a respiratory enzyme, providing energy to the cell, and as the main sodium pump, energizing the membrane and driving nutrient uptake, pH regulation, elimination of drugs, cell motility, secretion of toxins and other homeostatic processes. Na+-NQR is an optimal drug target due to its critical role in bacterial metabolism and because it is absent in mammalian cells. Moreover, Na+-NQR has unique structural motifs, not found in any human protein, which allow the discovery of drugs that can act specifically on this enzyme. In addition, Na+-NQR inhibitors could increase the susceptibility of V. cholerae to other drugs by de-energizing the membrane, and may be used in a combination dosing approach to rescue obsolete antibiotics. Our group has now identified two novel compound leads, ubiquinone analogs (UQAs) and phenothiazines, as inhibitors of this enzyme that are suitable for drug development. The three UQAs analogs characterized have antimalarial properties and show specific and potent inhibitory effects on Na+-NQR, with strong antibiotic activity against V. cholerae. These compounds not only abolish V. cholerae Na+-NQR enzymatic activity, but also trigger the overproduction of reactive oxygen species, which is lethal to microbes. The structures of these inhibitors and docking methods were used to identify the pharmacophore and the binding modes of the molecules in the UQ binding site, which allow us to pursue lead development to obtain inhibitors of high potency and specificity. In addition, we have identified three phenothiazine-like compounds with anti- psychotic properties that show potent inhibitory activity against Na+-NQR and that could be optimized into antibiotics. The main aim of this project is the development of a novel class of antibiotics to specifically target the Na+-NQR complex. The inhibitors that we have identified will be fully characterized, to understand their mechanism of action, binding sites, potency and antibiotic properties. Moreover, toxicity towards human cells and mitochondria, as well as their pharmacologic properties, will be assessed to evaluate the potential of these compounds to treat human infections. The data obtained from toxicity studies, enzymatic and microbiological characterizations will be used to guide the design and synthesis of analogs with high potency and low toxicity. Lead optimization will be carried out by our medicinal chemistry team guided by pharmacophore analysis, docking and binding free energy calculations. The structures of the newly-identified inhibitors will be used to build compound libraries carrying the active core with different substitution patterns, which will be iteratively screened and characterized. The data generated in this proposal is critical to the discovery of urgently-needed antibiotics with a new mechanism of action effective against V. cholerae and many other Na+-NQR bearing pathogens.

NIH Research Projects · FY 2026 · 2021-02

The Biophysics Collaborative Access Team (BioCAT) provides biomedical researchers with access to a state-of-the-art synchrotron beamline (18ID) at the Advanced Photon Source, Argonne National Laboratory optimized for diffraction and scattering of non-crystalline biological materials. Since first light in 1997, BioCAT has been a leader in this area, and now provides users with the strongest fiber diffraction program in the United States and a world-class solution small angle x-ray scattering (SAXS) program with unique time-resolved SAXS capabilities. BioCAT is a world leader in the study of muscle diffraction, and has enabled researchers to answer complex biological questions, from understanding the fundamental biophysics of muscle function to translational studies of cardiomyopathies. For SAXS, BioCAT focuses on providing the highest quality data, using highly automated liquid chromatography coupled SAXS and a coflow cell that essentially eliminates radiation damage, and high data density via coupled complementary biophysical techniques, enabling studies on the most challenging systems. The unique time resolved SAXS program provides users access to continuous flow mixing experiments with timepoints from ~45 µs to 1.5 s. A key factor in BioCAT's success is its highly experienced and dedicated scientific staff, who provide comprehensive support to users seven days a week and frequently collaborate with users both pre- and post-experiment to ensure the most successful possible measurements. Successful experiments at the beamline, and our YouTube channel and data analysis packages (BioXTAS RAW and MuscleX) receive tens of thousands of views and thousands of downloads from more than 100 countries. We offer remote access and mail-in experiments for users who cannot travel to the beamline and would otherwise be unable to access the facility. Looking to the future, BioCAT is committed to maintaining and expanding its cutting-edge capabilities to meet emerging research needs. We are continuously exploring new technological advancements and potential upgrades to ensure that our facility remains at the forefront of biophysical research. This includes our ongoing optical upgrades to take advantage of the new best-in-class APS-U source, advances in automation and new microfluidic mixers for SAXS, and novel cardiac muscle preparations for muscle fiber diffraction. Together, the bioSAXS and fiber diffraction programs at BioCAT support 90-100 user visits annually, leading to 30-40 publications each year. Our facility enables our users to both advance the fields of structural biology and biophysics and also address critical public health challenges by enabling groundbreaking research that informs the development of new therapies and diagnostic tools.

NIH Research Projects · FY 2024 · 2016-09

ABSTRACT The proposed work to clinically test an intracortical visual prosthesis under an FDA-approved Early Feasibility Study addresses both health and quality-of-life issues because, without some compensatory strategy for vision loss, over two thirds of individuals with blindness are not gainfully employed, they experience higher rates of depression and social isolation, and experience a reduced quality-of-life. For the past fifteen years, The Illinois Institute of Technology (IIT) has lead a team-based IntraCortical Visual Prosthesis (ICVP) project, consisting of multiple institutions and companies, to develop the ICVP Our entry point, for this project, is: the ICVP is technically and surgically feasible, non-human testing has reached an asymptotic limitation, volunteer participation in an ICVP trial has a sufficient likelihood of providing sensory, perceptual, and psychological benefits to warrant human testing, and, that our established ICVP team is prepared to proceed to a first human clinical trial. The proposed project will use the already well-established project team lead by Dr. Troyk at IIT. This team is comprised of researchers from seven institutions: Illinois Institute of Technology, University of Chicago (UC), Johns Hopkins University (JHU), University of Texas, Dallas (UTD), Sigenics, Inc, MicroProbes for Life Science (MLS), and the Chicago Lighthouse for People who are Blind or Visually Impaired (CLH).

NIH Research Projects · FY 2025 · 2016-09

Project Summary: Over the last two decades, enabled by progress in synchrotron radiation techniques, molecular biology methods, and computational resources, there has been tremendous progress in determining the conformations of biomolecules that has led to deep structural and functional insights. But there is another dimension to biological function, namely dynamics, which is, as yet, underexplored. This has created a serious blind spot that inhibits progress towards a full understanding of macromolecular functions and biological processes. The broad objective of this proposal is to utilize and develop computer simulations that address this deficiency in knowledge by rigorously modeling biomolecular dynamics to increase our understanding of biological processes. More specifically, we will pursue three interrelated projects. First, we will determine how chromatin remodeling factors influence the dynamics of nucleosomes and chromatin fibers as a means of epigenetic gene regulation. Second, we will examine the mechanisms of key virulence factors in bacteria, including how they scagence iron from hosts and how they defended themselves from peptidomimetics. Finally, we will develop computational methods that more effectively model the results of solution small angle X-ray scattering experiments for diverse biomolecular complexes. Completion of these studies will reveal intricate details about the relationship between the structure, function, and dynamics of multicomponent biomolecular complexes across a vast range of time and length scales. Furthermore, the synergy between the scientific goals, as well as the computational methods and strong experimental collaborations in each of these projects, will foster new opportunities and areas of scientific inquiry that the MIRA award will allow us to pursue. Overall, this work will address a series of fundamental gaps in knowledge for critical biological processes, and will lay the foundation for future studies that will improve the treatment and prevention of human ailments.

NIH Research Projects · FY 2025 · 2014-09

The Institute for Food Safety and Health (IFSH) National Center for Food Safety and Technology (NCFST) housed at Illinois Institute of Technology (Illinois Tech) is a food safety and applied nutrition research consortium of the US Food and Drug Administration's Center for Food Safety and Applied Nutrition (FDA/CFSAN), Illinois Tech, and the food industry. Since the establishment in 1988, NCFST has successfully been providing a unique collaborative neutral ground where scientists with food safety and technology expertise from academia, government, and industry join forces and work together to address food safety, food defense, and nutrition issues of national significance. The successful results of the past 35 years by the NCFST are due to this collaborative way of working. NCFST is structured so that representatives of participating organizations play a role in helping establish policy and administrative procedures, as well as identifying long- and short-term research programs that address FDA and industry strategic needs. With this organizational structure, NCFST is uniquely positioned to build cooperative food safety programs on a foundation of knowledge about current industrial trends in food processing and packaging technologies, regulatory perspectives from public health organizations, and fundamental scientific expertise from academia. The NCFST collaborative research programs are coordinated through various inputs by participating representatives throughout the year. This includes regular meetings with the Executive Advisory Board, the Science Advisory Committee, and various Science Forums advising and recommending research topics in the five research platforms including Processing, Microbiology, Food Chemistry and Packaging, Proficiency Testing and Method Validation Research, and Nutrition. With an increasingly diverse domestic and global food supply, FDA continues to face complex food safety challenges associated with foods that it regulates. In 2011, the enactment of the FDA Food Safety Modernization Act (FSMA) emphasized the need for a modern, prevention-based food safety system. Through the IFSH research consortium all parties work to help form a scientific basis for policy decisions affecting food safety and public health. In addition, NCFST is the coordinator of the Food Safety Preventive Controls Alliance (FSPCA), the Sprouts Safety Alliance (SSA), and the Juice HACCP Alliance, leveraging the expertise of academia, industry, and FDA for the purpose of developing and delivering standardized curricula related to FSMA requirements. The outreach on preventive controls provided by these Alliances strengthens integral parts of the FDA's FSMA implementation strategies. IFSH will continue to carry out multidisciplinary applied research; leverage collaborations with government, academia, and the food industry; develop and implement outreach and communications programs with stakeholders; and support the continued implementation of FSMA.