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therapeutics and medical devices faculty summaries and technology abstracts for more information contact sonia kim phd manager for marketing and industry partnerships innovation and new ventures office 1800 sherman ave suite 504 evanston il 60201 main 847 467-2097 direct 847 467-0446 email invo@northwestern.edu or sonia.kim@northwestern.edu 1

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contents therapeutics metabolic syndromes douglas vaughan md 8 treatment of diabetes using combination therapy of ppar agonists and soluble epoxide hydrolase inhibitors 8 cdt project douglas vaughan md mesut eren phd and sheila murphy pai-1 deficiency protects against accelerated aging in klotho-deficient mice 8 joseph bass md phd 9 mouse model for endocrine pancreatic development insulin secretion and diabetes 9 stephen d miller phd 10 modulation of immune function by the targeted enhancement of cd154 trimer stability 10 oncology center for developmental therapeutics cdt 11 andrew mazar phd 11 thomas o halloran phd 11 cdt project thomas o halloran phd and andrew mazar phd urokinase plasminogen activator upa and urokinase plasminogen activator receptor upar targeted agents for the treatment of cancer 12 cdt project douglas vaughan md and andrew mazar phd therapeutic targeting of pai-1 in diseases like cancer acute lung fibrosis intravascular thrombosis and polycystic ovarian syndrome 12 glioma brain tumor alexander stegh phd 13 breast cancer sui huang md phd 13 cdt project metastatic cancer diagnostic and related therapeutics 13 jacqueline jeruss md phd 14 cdt project impact of cdk inhibition on cyclin overexpressing breast cancers 14 serdar bulun md and irene moy md susd3 a target for prevention diagnosis and treatment of estrogen/progesterone-dependent disorders 15 2

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pancreatic cancer jack henkin phd cdt project targeting tumor cell cd74 via toxic conjugates of its natural ligand mif-1 15 prostate cancer raymond bergan md 16 karl scheidt phd 16 cdt project karl schiedt phd and raymond bergan md novel inhibitors of mek4 and prostate cancer metastasis 16 irina budunova md phd 17 cdt project compound a to treat androgen-dependent diseases with inflammatory component like prostate cancer 17 high throughput proteomic platform neil kelleher phd 18 novel chemistry new linkers malathy shanmugam phd 18 treatment of multiple myeloma using fda-approved hiv drug 18 steven rosen md 18 cdt project steven rosen md and malathy shanmugam phd targeting atypical glucose transporter expression for the treatment of multiple myeloma and glucose-dependent cancers 19 fibrosis wound repair mike abecassis md 19 jonathan jones phd 19 2a3 antibody an anti-angiogenic antibody against 4 laminin 20 monoclonal antibodies for laminin-5 and hemidesmosomes 20 cdt project jonathan jones phd and kevin hamill phd targeting a novel family of laminin-related proteins as a means of regulating tissue remodeling in wound healing and cancer 21 scleroderma john varga md 21 feng fang phd 21 cdt project john varga md and feng fang phd small molecules targeting egr2 signaling for fibrosis disease 22 3

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surgical adhesions phil messersmith phd 22 robust antifouling hydrogels and coatings 22 lonnie shea phd 23 opthalmology olga volpert phd 23 cdt project fine mapping of pigment epithelium-derived factor anti-angiogenic activity 24 andrew mazar phd immuno-inflammation copd gregory beitel phd 24 peter sporn md 24 david kamp md 24 auto-immunity stephen miller phd syamal datta md very low dose tolerance with nucleosomal peptides controls lupus and induced potent regulatory t-cell subsets 25 immunotherapy daocheng zhu md phd 25 paul bryce phd 25 leslie grammer,md 25 robert schleimer phd 26 cdt project daocheng zhu md phd paul bryce phd leslie grammer md robert schleimer phd immunotherapy for peanut allergy with allergen-fc fusion protein 26 neurological disease alzeimer s disease/parkinson s disease jim surmeier phd 26 manipulation of neuronal ion channels as a treatment for parkinson s disease 27 richard silverman phd 27 novel peptide compounds with selective inhibition of neuronal nitric oxide synthase 27 novel peptide compounds with enhanced anti-tumor activity 28 highly potent and selective neuronal nitric oxide synthase inhibitors with improved membrane permeability 29 4

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cdt project potent and selective inhibitors of neuronal nitric oxide synthase for the treatment of neurodegenerative diseases like alzheimer s and parkinson s 29 lester binder phd 30 tau-13 monoclonal antibody to tau 30 tau-c3 monoclonal antibody specific to tau truncated at aspartic acid 421 30 tau-12 monoclonal antibody specific to the n-terminus of tau 31 tau-ny29 monoclonal antibody specific to tau nitrated at tyrosine 29 31 tau-ny18 monoclonal antibody specific to tau nitrated at tyrosine 18 32 tau-7 monoclonal antibody specific for the c-terminus of tau 32 amyotropic lateral sclerosis teepu siddique md 33 transgenic mice expressing superoxide dismutase 33 small molecule down-regulation of cu zn-superoxide dismutase expression 33 thomas j lukas phd 34 cdt project teepu siddique md and thomas lukas phd etiological-based approach to treatment of familial amyotrophic lateral sclerosis 34 depression dane chetkovich md phd 35 cdt project identification of small molecule inhibitors of hcn channel function in depression 35 infectious disease karl scheidt phd thomas o halloran phd andrew mazar phd cdt project thomas o halloran phd and andrew mazar phd new therapeutic approaches to the treatment of infectious diseases by disrupting metal trafficking pathways 36 vaccines david j klumpp phd 36 anthony schaeffer md 37 cdt project david j klumpp phd and anthony schaeffer md microbial modulation of immunity and pain 37 platform opportunities shad thaxton md phd 37 scanometric-based microrna profiling array using polyvalent dna-gold nanoconjugates 38 dean ho phd 38 novel molecular imaging probes using gdiii nanodiamond conjugates 39 teri odom phd 39 5

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medical devices vascular surgery melina kibbe md 40 liquid cast biodegradable drug delivering arterial stent 40 cardiovascular surgery patrick m mccarthy md 41 rishi arora md 41 a novel cardiovascular catheter for targeted gene therapy 41 plastic surgery thomas mustoe md and robert galiano md 42 biodesign fellowship elliot m hirsch md alberto colombo phd and anandev gurjala md leak resistant detachable fluid conduit connector 43 implant introducer 43 gastrointestinal surgery nathaniel j soper md 44 david mahvi md 44 interventional radiology reed omary md and andrew larson phd 44 magnetic labeling of radioactive microparticles for electromagnetic therapy 45 ob/gyn and women s health 45 lonnie shea phd 45 interpenetrating semi-degradable fibrin-alginate hydrogels 45 carla m pugh md phd 46 new biomaterials antibacterial phillip b messersmith phd 46 igal szleifer phd 47 bartosz a grzybowski phd 47 novel single-dip method for producing antibacterial and other electrostatic metal-based surface coatings 48 6

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tissue support and soft tissue repair/replacement guillermo ameer scd 48 ramille shah phd 49 arun sharma phd 50 model for urinary bladder regeneration utilizing autologous sources of bone marrow derived mesenchymal stem cells 50 general medical device and design resources mitra hartmann phd 51 chang liu phd 51 center for simulation technology and immersive learning 52 segal design institute 53 pre-ip project 54 jack henkin phd thrombospondin-1 agonists william mueller md phd interference of hsv glycoprotein gd interaction with nectins david kamp md ogg1 mimetics harris perlman,phd bim mimetic peptide start-up companies with northwestern ips acumen pharmaceuticals 55 aurasense 55 nanocytomics 55 nanotope 55 naurex 55 proteostasis therapeutics 56 rhythmos therapeutics 56 transition therapeutics 56 vesseltek biomedical 56 viamet pharmaceuticals 56 pending start-up companies with northwestern ips new co 57 serpentine therapeutics 57 prepared december 16 2011 7

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therapeutics metabolic syndromes douglas vaughan md irving s cutter professor of medicine and chair department of medicine feinberg school of medicine dr vaughan s research involves the study of hormonal factors that influence the risk of arterial thrombosis and its implications go beyond traditional specialties he is internationally known for his work in vascular biology which focuses on the plasminogen activator system in cardiovascular disease treatment of diabetes using combination therapy of ppar agonists and soluble epoxide hydrolase inhibitors abstract northwestern researchers have identified methods involving combination therapy for diabetes and diabetesrelated diseases in this therapy peroxisome proliferator-activated receptor gamma ppar is activated and soluble epoxide hydrolase is inhibited while ppar-activating agents are crucial to the treatment of diabetes as it reduces insulin resistance in cells it also has problematic adverse effects when co-administered with insulin namely edema and weight gain by utilizing the proposed combination therapy with soluble epoxide hydrolase inhibitors inflammation and hypertension are ameliorated and anti-hypertensive antiinflammatory and anti-diabetic effects are more pronounced applications therapeutics diabetes and metabolic disease treatment for fluid retention e.g edema congestive heart failure advantages diminished risk for edema and/or congestive heart failure pronounced anti-hypertensive anti-inflammatory and anti-diabetic effects ctd project douglas vaughan md mesut eren phd and sheila murphy pai-1 deficiency protects against accelerated aging in klotho-deficient mice abstract northwestern researchers have identified a target that may have beneficial effects in delaying age-related properties the klotho gene encodes a single-pass transmembrane protein and functions as an agingsuppressor gene extending life span when overexpressed in its absence mice exhibit accelerated development of aging-like phenotypes including a markedly truncated lifespan infertility osteoporosis renal sclerosis and obstructive pulmonary disease the biochemical hallmarks of these mice include elevated plasma levels of fgf23 phosphate calcium vitamin d and plasma pai-1 the researchers found that the codeficiency with pai-1 attenuates the phenotype of the klotho-deficient mice the double-knockouts no longer display a significant elevation in serum levels of calcium phosphate and creatinine they also exhibit normal fertility most notable is that the additional absence or partial absence of pai-1 doubles the lifespan these 8

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results suggest that drugs that either directly or indirectly reduce pai-1 may have beneficial effects in delaying age-related pathologies application drug discovery for aging advantages existing in vivo model extended life span delayed aging phenotype joseph bass md phd associate professor in neurobiology and physiology feinberg school of medicine dr bass long-term research goals are to delineate brain pathways involved in control of behavior and metabolism and to develop high-throughput approaches to identify targets for anti-hyperglycemic and anti-obesity therapies specifically the bass lab recently discovered that mutation of the gene encoding the transcription factor clock present within the brain and peripheral metabolic tissues leads to altered sleep feeding activity obesity and diabetes these studies prompted the search for targets of the clock gene network and a major focus of his lab is 1 to delineate function of the clock gene network in the regulation of pancreatic islet cell development and insulin exocytosis and 2 function of the hypothalamic clock in response to appetitive hormones and peripheral metabolism mouse model for endocrine pancreatic development insulin secretion and diabetes abstract northwestern researcher joseph bass created a mouse model based on removing the clock function within islet cells these mice exhibit striking defects in insulin secretion which ultimately leads to greatly accelerated early life diabetes this model provides a direct opportunity to apply new methods to study and understand how the clock transcription network regulates aspects of endocrine pancreas function with this understanding it provides the opportunity to explore various means of enhancing islet function and to further develop existing or potential therapies for diabetes such as 1 stem cell therapies for type 1 diabetes 2 cell survival in post-transplant and/or endogenous islet function in type 1 and 2 diabetes and 3 pharmacotherapeutic targeting for enhanced insulin secretion in type 2 diabetes in fact the development of clock-modulators using this platform is already underway applications research tool animal model o high throughput screening for diabetes-modifying therapeutics o identification of methods using stem cell transplantation and cell preservation methods o drug discovery for improved combination treatments with existing agents advantages powerful tool to dissect the role of clock transcription network on endocrine pancreas function stephen d miller phd professor in microbiology-immunology feinberg school of medicine 9

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dr miller investigates the cellular and molecular mechanisms of multiple aspects of the immunopathogenesis and specific immunoregulation of t cell-mediated autoimmune responses employing a virus-induced model of multiple sclerosis and an autoimmune model of multiple sclerosis modulation of immune function by the targeted enhancement of cd154 trimer stability abstract northwestern researchers have developed a new therapy that can either inhibit immune cell function in autoimmune disease or enhance natural or vaccine-facilitated immune responses they have identified a small molecule that can modulate the immune response by stabilizing an active but transient cd154 trimer which is central to a type 1 helper t-cell immune response and immune effector function they screened over 250,000 compounds for the ability to bind the cd154 trimer and found two candidates that had the ability to stabilize the trimer in vivo it was successful in a mouse model demonstrating the ability of the compound to enhance an immune response further results in a mouse cancer model also show promising results in both tumor reduction and decreased metastasis applications vaccine therapy protect against infectious or toxic agents therapeutics autoimmune disease cancer infectious disease immunotherapy advantages successful mouse model immune response and cancer therapy applicable to multiple diseases 10

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oncology center for developmental therapeutics the center of developmental therapeutics cdt was founded in 2009 with the mission of becoming an entry portal for pre-clinical drug development operating under the leadership of its founding director dr andrew mazar it has initially focused on cancer drug development and is expanding beyond the robert h lurie comprehensive cancer center rhlccc to serve all clinical and basic sciences researchers in the nu community this would significantly enhance the medical mission of the university and would serve to advance the one northwestern initiative the main objectives of cdt internally are to identify and assist with development on internal translational projects as well as on external projects that are of interest to northwestern investigators cdt also assists in the initiation and advancement of new spin-out companies working on nu technologies or on collaborations with other universities and industry andrew mazar phd entrepreneur-in-residence chemistry of life processes institute director center for developmental therapeutics and research professor of molecular biosciences weinberg college of arts and sciences dr mazar is internationally recognized for his basic research work on the role of the urokinase plasminogen activator upa system in tumor progression and angiogenesis in addition he has led r&d at two start-up companies and has been responsible for advancing numerous drug candidates from discovery through mid-stage clinical trials thomas o halloran phd charles e and emma h morrison professor of chemistry professor of molecular biosciences weinberg college of arts and sciences director chemistry of life processes institute associate director for basic sciences research robert h lurie comprehensive cancer center of northwestern university dr o halloran s research centers on the regulatory biology and chemistry of transition metal receptors involved in homeostasis and oxidative stress pathways his laboratory focuses on nanoscale drug delivery mechanisms and on the mechanisms of clinically important anticancer agents that are based on arsenic molybdenum and platinum chemistry this work has led to the discovery of new classes of soluble metal receptors metalloregulatory and metallochaperone proteins most recently he discovered nanoscale processes for targeted delivery of multifunctional therapeutic agents for treatment of hematological cancer and solid tumors these agents are moving rapidly towards clinical trials 11

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cdt project thomas o halloran phd and andrew mazar phd urokinase plasminogen activator upa and urokinase plasminogen activator receptor upar targeted agents for the treatment of cancer abstract northwestern researchers have developed a therapeutic approach to treating cancer using the urokinase plasminogen activator upa system upa and its receptor upar are selectively expressed in most solid tumors with very little expression observed in normal quiescent tissues in humans thus making these ideal tumor targets for the delivery of cancer therapeutics they have already identified a number of upa and upartargeting antibodies with different properties including the ability to be internalized to bind to ligand-bound upar and to bind the fragments of upar that are typically observed on tumor cells prior research indicates that nanoparticles that are directly targeted to cancer antigens have exhibited greater antitumor activity in the same manner these upa-targeted agents can be conjugated to any drug for tumor-specific delivery the investigators envision coupling their targeting and nanoparticle approaches with agents of interest for targeted tumor therapy applications therapeutics anti-cancer advantages tumor-specific delivery ability to customize cytotoxic formulations specific for tumor types extensive expertise in nanoparticle cytotoxin formulations developed all relevant assays and screens prepared prototypes that are robustly taken up by upar-expressing tumor cells funding uses targeted tumor therapy coupling our targeting and nanoparticle approaches with agents of interest antibody humanization process development and other development activities associated with ind-enabling studies estimated budget $200k/yr cdt project douglas vaughan md and andrew mazar phd therapeutic targeting of pai-1 in diseases like cancer acute lung fibrosis intravascular thrombosis and polycystic ovarian syndrome abstract northwestern researchers have identified a target for the treatment of dysregulated fibrinolysis which has been implicated in a number of disease processes including cancer acute lung fibrosis intravascular thrombosis and polycystic ovarian syndrome they found that an increase in plasminogen activator inhibitor-1 pai-1 shifts the fibrinolytic balance towards inhibition in these fibrotic diseases having identified pai-1 as a target for treating dysregulated fibrinolysis they are now interested in discovering a small molecule inhibitor of pai-1 that can regulate thrombosis and fibrosis the investigators have utilized a number of models constitutively active pai-1 transgenic models of thrombosis models of organ-specific fibrosis set up to evaluate pai-1 inhibitors that will help guide a decision on the clinical indication they have already tested several lead modestly potent pai-1 inhibitors and demonstrated some biological activity further confirming the 12

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utility of targeting pai-1 therapeutically they have also used both in silico and in vitro assays in parallel to identify additional pai-1 inhibitor leads an initial in silico screen of 27000 structures using refined pai-1 structures identified 8 hits after scoring filtering and clustering one of these was tested in an in vitro assay and showed promising pai-1 inhibitory activity at 50 m applications therapeutic small molecule for inhibition of fibrotic diseases funding uses compound libraries screening and assay support drug development consulting estimated budget $200k/yr glioma brain tumor alexander h stegh phd assistant professor in neurology feinberg school of medicine dr stegh s research program is aimed at understanding the genetic program that underlies the pathogenesis of glioblastoma multiforme gbm the most prevalent and malignant form of brain cancer specifically he focuses on the functional validation and ultimately the therapeutic modulation of novel oncogenes and tumor suppressors implicated in the genesis of malignant glioma breast cancer sui huang md phd associate professor in cell and molecular biology feinberg school of medicine dr huang is interested in the functional significance of nuclear compartmentalization in gene expression regulations at normal and diseased conditions specifically she focuses on two nuclear organelles the nucleolus where ribosome synthesis takes place and the pnc whose formation is associated with malignancy cdt project metastatic cancer diagnostic and related therapeutics abstract a northwestern researcher has identified and developed new small molecular drug candidates that target the perinucleolar compartment pnc the pnc has already been shown to correlate with the degree of malignancy in breast and other cancers and can be easily identified by tissue staining elisa and flow cytometry the development of several antibodies that detect pnc further facilitates its identification in addition to diagnostic capabilities these novel compounds also show both in vitro and in vivo anti-cancer capabilities applications diagnostic breast cancer therapeutic breast cancer 13

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advantages easy to detect existing tools related to pnc jacqueline jeruss md phd assistant professor in surgery-surgical oncology feinberg school of medicine dr jeruss research focuses on how alterations in cell signaling affect breast cancer prognosis specifically the jeruss lab is working to further understand the mechanism by which smad 3 acts to inhibit breast cancer growth and development and to identify the mechanism of inactivation of the smad 3 protein cdt project impact of cdk inhibition on cyclin-overexpressing breast cancers abstract northwestern researchers have developed their search cdk inhibitors for drug development in treating breast cancer that overexpress cyclins growing research points to the tgf superfamily member smad3 as a tumor suppressor in breast cancer which is inhibited by cyclin/cdk activity the investigators have completed in vitro studies examining the impact of cdk2 and cdk4 inhibitors alone and in combination with chemotherapy on cell proliferation in estrogen receptor er and er cyclin-overexpressing breast cancer cell lines they have also performed these experiments using 3d tumor culture and are now beginning studies using a murine model while a pan cdk inhibitor is currently being employed in clinical trials for both solid tumors and hematogenous malignancies and several other cdk inhibitors have also been studied to date no specific cdk4 or cdk2 inhibitor has been generated and applied specifically to the irradiation of breast cancers that overexpress cyclins applications therapeutics anti-cancer use in conjunction with radiation therapy funding uses drug development consulting for the discovery of specific cdk4 and cdk2 inhibitors including the reagents to design these inhibitors estimated budget $100,000 14

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serdar bulun md and irene moy md susd3 a target for prevention diagnosis and treatment of estrogen/progesterone-dependent disorders abstract bulun and moy have identified a novel cell surface receptor for estrogen which mediates estrogen uptake by tumor and endometrial cells they are identifying monoclonal antibodies that inhibit the estrogen uptake and may circumvent toxicities of estrogen receptor or pathway antagonism pancreatic cancer jack henkin phd visiting scholar center for developmental therapeutics cdt project targeting tumor cell cd74 via toxic conjugates of its natural ligand mif-1 abstract northwestern researchers have identified a drug target for anti-tumor compounds receptor cd74 is rare on normal cells but highly enriched on the surface of cancer cells especially lymphomas and solid tumors in response to stress the investigators show that a fluorescently tagged mif-1 which binds to cd74 is rapidly internalized in vivo into tumors that express this receptor intracellular fluorescence accumulates within minutes in vitro and within an hour in vivo the researchers are working to administer established or proprietary anti-tumor compounds that are conjugated to a unique reactive amino acid residue on mif-1 that will mediate tumor cytotoxicity following a few hours of plasma exposure application drug delivery anti-cancer chemotherapy advantages tumor-specific receptors rapid uptake use of fluorescent microscopy to visualize in vitro and in vivo models funding uses creation of compound library organic synthesis to couple with linkers pilot scale up of mif protein expression and conjugation pk and safety testing tumor cell screens and tumor models estimated budget $109,000 15

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