Vaccibody has developed a unique platform technology able to substantially potentiate vaccines by an inherent mechanism that attract, activate and deliver antigens to antigen presenting cells. Currently, Vaccibody is heavily focusing on using the platform technology to generate unique individualized cancer neoantigen vaccines. Recent clinical data indicate an important role of T cell immunity to cancer neoantigens in patients that benefit from immunotherapies. A cancer neoantigen vaccine should be customized for each individual patients cancer-specific somatic mutations and hence warrant manufacturing of one vaccine per patient. By using the DNA vaccine format encoding for the Vaccibody protein, a rapid, cost-effective and robust manufacturing process has been generated which lends itself perfectly to develop commercially viable patient-specific vaccines on demand. Supportive preclinical data with neoantigen based DNA vaccines as well as clinical data with a similar Vaccibody DNA vaccine using viral antigens support a favourable safety, tolerability and efficacy profile. A clinical study using targeted Vaccibody neoepitope DNA vaccines in multiple advanced cancer indications is planned to start Q1 2018.

Heart failure (HF) is a major problem for our contemporary societies in terms of prevalence, mortality and cost. Natriuretic peptides are recognized biomarkers for the diagnosis of HF but also for risk stratification. Innovative biomarkers are studied to improve the sub-phenotyping of HF, to facilitate the diagnosis of HF with preserved ejection fraction, and to tailor therapeutic approaches. The soluble receptor of interleukin 33 (sST2) is one of these new biomarkers. In groups of patients at higher risk of HF (hypertension, diabetes), measurement of sST2 could identify patients requiring more sustained management. In the case of HF with reduced ejection fraction, sST2 would be a powerful marker for risk estimation but also to confirm treatment choice. In the case of HF with preserved ejection fraction, measurement of sST2 may be useful for confirming a diagnosis but also for the risk stratification of the patients and as companion marker for the treatment. Interestingly, the determination of the concentrations of sST2 is facilitated by the evolution of assays with new point of care testing methods. As for many innovative biomarkers, the transition of sS2T to routine testing requires strong multidiscilplinary exchanges with physicians.

The path form biomarker discovery to conversion to a clinically useful companion diagnostic test presents many challenges. The talk will outline the regulatory requirements to developing a successful companion diagnostic test and the challenges that are encountered during the process. 

Pharmacogenomics has emerged as an early use case of precision medicine.  Delivering this new clinical data to clinicians in a ready to use format can be challenging.  This talk will cover key decision points and components needed for a systemic-wide implementation of pharmacogenomics.  NorthShore University HealthSystem’s Personalized Medicine Program will be used as an example to highlight a number of these concepts.  This talk should help the attendee begin to formulate a plan for implementation.

G-protein coupled receptors (GPCRs) represent the single largest class of druggable targets in the human genome. Of the 390 or so druggable and non-olfactory human GPCRs there exist many which are orphan and/or understudied; we refer to these as "oGPCRs". In this talk I will show how new technologies developed by my lab can illuminate the pharmacology, signaling pathways, chemical biology, distribution and function of GPCrs. I will highlight our new open-source tools which include  open-access repositories of chemical probe molecules, reporter plasmids and engineered animals that enable investigators to interrogate the biological functions of GPCRs. Given the central importance of GPCRs for all areas of biomedical research, illuminating the pharmacology, function, signaling and chemical biology of known GPCRs and oGPCRs will have far-reaching impact for both therapeutics and basic biomedical science.

Preterm birth (PTB) is the leading cause of infant mortality and morbidity worldwide. Both preterm labor and neonatal injuries have been linked to inflammation. Of all mediators of inflammation, the major pro-inflammatory cytokine IL-1ß has been shown to trigger a specific pattern of gene expression in uterus and placenta resulting in PTB and in neonatal organ injury and significant fetal demise. Here, we show that a small peptide noncompetitive IL-1R antagonist (rytvela, labeled 101.10) designed and characterized by us, exerts potential therapeutic efficacy in preventing PTB and improving neonatal outcome. Effects of 101.10 were compared to a clinically available IL-1R competitive antagonist (Kineret). Our results show that 101.10 selectively inhibits the downstream stress-associated factors JNK, p38 and c-jun and the small GTPase Rho in myometrial smooth muscle cells and uterine explants and desirably does not interfere with the transcription factor NF-kB activity. Administration of 101.10 to pregnant mice revealed efficacy in preventing IL-1ß-, LTA- and LPS-induced PTB by down-regulating a series of proinflammatory mediators in uterus, placenta, fetal membranes, maternal circulating white blood cells and amniotic fluids. In pregnant mice treated with IL-1ß, 101.10 increased neonatal survival, and this was associated later in life with improved tissue (lung, intestine and brain) analyzed by histology. Specifically, 101.10 protected against IL-1ß-induced cerebral microvascular degeneration, loss in brain mass, which resulted in improved amplitude and latency of visual evoked potential, suggesting normalized brain function reflected in preservation of synaptic transmission through the brain of pups. In LPS-induced PTB (which mimic a gram – infection during pregnancy), 101.10 also increased neonatal survival in addition to decreasing the expression of proinflammatory mRNA transcripts in brain. 101.10 conveyed superior or comparable efficacy to Kineret in all assays performed; Kineret was largely ineffective at prolonging preterm gestation or improving neonatal outcomes, as already reported by other groups. In summary, our data describe a new potential therapeutic candidate that selectively modulates IL-1R-related signaling (thereby preserving NF-?B activity) which is effective in preventing the onset of PTB and associated adverse neonatal outcomes.

There is an acute shortage of organs due to disease, trauma, congenital defects, and most importantly, age related maladies. The synthetic materials used in tissue engineering applications today are typically composed of millimeter or micron sized particles and/or fiber dimensions. Although human cells are on the micron scale, their individual components, e.g. proteins, are composed of nanometer features. By modifying only the nanofeatures on material surfaces without changing surface chemistry, it is possible to increase tissue growth of any human tissue by controlling the endogenous adsorption of adhesive proteins onto the material surface. In addition, our group has shown that these same nanofeatures and nano-modifications can reduce bacterial growth without using antibiotics, which may further accelerate the growth of antibiotic resistant microbes. Inflammation can also be decreased through the use of nanomaterials. Finally, nanomedicine has been shown to stimulate the growth and differentiation of stem cells, which may someday be used to treat incurable disorders, such as neural damage.  This strategy also accelerates FDA approval and commercialization efforts since new chemistries are not proposed, rather chemistries already approved by the FDA with altered nanoscale features. This invited talk will highlight some of the advancements and emphasize current nanomaterials approved by the FDA for human implantation.  

Structure based drug design is now well established as a highly efficient approach in pharmaceutical research.  The approach uses atomic level detail structures of target proteins, most generally determined through X-ray crystallography. For many years this approach has not been possible for the most common classes of drug targets, particularly membrane bound proteins such as GPCRs and transporters. Approximately 10 years ago, the first X-ray structures in these areas started to emerge and the determination of more structures has begun to accelerate in the recent past. These structures cover a rapidly increasing number of targets and categories including class A, B, C and F GPCRs, endogenous amine transporters. Included in these reports are proteins in various states, novel sites for ligand modulation and other characterizations. These reports have provided valuable information facilitating the design of new compounds with specific features such as intrinsic activity (from active to inactive), ligand bias, selectivity, allosterism and others. This growing body of information will be illustrated along with examples of successes and emerging new opportunities.

GPCRs constitute the largest receptor family in the human genome. Over the years they have proven themselves to be druggable targets accounting for about 1/3 of all drugs on the market today.  Of these, approximately 15% have been approved by the US Food and Drug Administration (FDA) in the last 5 years.  Recent GPCR drug discovery efforts are expanding the range of disease indications to include polycystic ovarian syndrome, gastroparesis, pulmonary fibrosis, and smoking cessation. This talk will cover some of the novel targets, such as the calcitonin gene-related peptide (CGRP) receptor, the bile acid receptor GPBAR, the hydroxycarboxylic acid (HCA2 and HCA3) receptors, and orphan GPCRs such as GPR119.  Also covered will be the development of antibody-based therapeutics for GPCRs such as mogamulizumab for the chemokine receptor CCR4. 

We recently reported that HDAC6 is involved in the regulation of a number of immunosuppressive checkpoint proteins, including the Program Death Receptor Ligand 1 (PD-L1). This protein is one of the natural ligands for the PD-1 receptor present on T-cells, consistently reported to suppress T-cell activation, proliferation, and induce T-cell exhaustion, anergy and apoptosis. As a result, increased PD-L1 expression by cancer cells remains a fundamental escape mechanism from host immunity within the tumor microenvironment, and the understanding the molecular mechanisms modulating PD-L1 and other immunosuppressive mediators could lead to improved treatments for cancer patients. Several publications have linked the over-expression of PD-L1 in tumors and tumor microenvironment with a poor prognosis in several malignancies, including melanoma, ovarian, gastric and breast cancer, among many others. However, more detailed mechanistic information regarding the molecular events involved in the regulation of PD-L1 is still missing. Moreover, limited information is available about the participation of preclinical and clinical anti-cancer agents in the regulation of PD-L1 and other immunomodulatory pathways. As a result, this gap in knowledge is preventing the design of new immunotherapeutic combination therapies. Given the fact that HDAC6 is a potential regulator of immunosuppressive mediators, it opens up a new avenue for immunotherapy. By using selective HDAC6inh as adjuvants to ongoing immune blockade based treatments, we are aiming to further augment anti-tumor immune responses.   

This lecture introduces the evolving paradigm of Molecular Pathological Epidemiology (MPE) as simply as possible.  Any given human disease represents fundamentally heterogeneous process, as implicated by the "unique disease principle".  MPE dissects complex interplay between environment, lifestyle factors, molecular pathogenic alterations, and disease occurrence and progression, using large populations.  MPE is a logical next step of genome-wide association studies (GWAS), termed “GWAS-MPE Approach”.  MPE has proven itself to be a promising approach to identify biomarkers for precision medicine (Chan A et al. NEJM 2007; Liao X et al. NEJM 2012; Nishihara R et al. NEJM 2013, etc.).  Recently, the "pharmaco-MPE" paradigm (Ogino S et al. npj Prec Oncol 2017) has been utilized to uncover effects of medications on health and diseases.  In addition, the "immuno-MPE" approach integrates immunology and MPE, to decipher effects of environment on immune status in health and diseases.  It is increasingly critical to design large-scale population-based MPE databases worldwide by means of integrating medication use, lifestyle factors, molecular pathology, immune status, and clinical outcome.  Such databases can generate novel information on potential chemopreventive or therapeutic benefits of drugs, which can be further tested by experimental models and clinical trials.  To expand opportunities and address challenges, the "International Molecular Pathological Epidemiology (MPE) Meeting Series" was established in 2013, and the Fourth International MPE Meeting will be held in Boston in 2018 (May 31 to June 1).  Because disease heterogeneity is a ubiquitous phenomenon, the MPE concept should be widespread to advance biomedical and population health sciences in the 21st century, and move us towards precision prevention and treatment. 

Precision medicine allows for prediction of drug response and tailoring drug therapy based on genetic variability. This talk will provide examples of precision medicine initiatives at the University of Florida Health. Outcomes specific to CYP2C19 genotype-guided antiplatelet therapy will be described as will other efforts to examine outcomes with pharmacogenomic implementations.

Vaccibody has developed a unique platform technology able to substantially potentiate vaccines by an inherent mechanism that attract, activate and deliver antigens to antigen presenting cells. Currently, Vaccibody is heavily focusing on using the platform technology to generate unique individualized cancer neoantigen vaccines. Recent clinical data indicate an important role of T cell immunity to cancer neoantigens in patients that benefit from immunotherapies. A cancer neoantigen vaccine should be customized for each individual patients cancer-specific somatic mutations and hence warrant manufacturing of one vaccine per patient. By using the DNA vaccine format encoding for the Vaccibody protein, a rapid, cost-effective and robust manufacturing process has been generated which lends itself perfectly to develop commercially viable patient-specific vaccines on demand. Supportive preclinical data with neoantigen based DNA vaccines as well as clinical data with a similar Vaccibody DNA vaccine using viral antigens support a favourable safety, tolerability and efficacy profile. A clinical study using targeted Vaccibody neoepitope DNA vaccines in multiple advanced cancer indications is planned to start Q1 2018.

Pharmacogenomics has emerged as an early use case of precision medicine.  Delivering this new clinical data to clinicians in a ready to use format can be challenging.  This talk will cover key decision points and components needed for a systemic-wide implementation of pharmacogenomics.  NorthShore University HealthSystem’s Personalized Medicine Program will be used as an example to highlight a number of these concepts.  This talk should help the attendee begin to formulate a plan for implementation.

There are many tumor biomarkers but, they mostly reflect tumor mass or past growth, when what is more important is to obtain an indication of future growth and therapy response.

Proliferation biomarkers e.g. KI67, are mostly immunohistological biomarkers which limits their use. The ability to measure a proliferation biomarker in an easily available body fluid could reduce this problem and provide new opportunities for studying tumor growth and therapy response. 

Thymidine Kinase 1 (TK1) has the potential to be such as biomarker. 

This presentation will demonstrate how the immunoassay of TK1, using a unique monoclonal antibody directed against the TK 210 epitope (AroCell TK 210 ELISA) can provide new opportunities for the study of tumor growth, therapy response and in-vitro modelling of drug effects.

Thymidine Kinase 1 (TK1) is a key enzyme in DNA synthesis and it is up-regulated in the S phase of cell growth. It is released into the extracellular medium and, eventually, the blood during cell turnover.

TK1 enzyme activity has been used for many years as a biomarker for hematological malignancies but the complexity of the assay, plus the fact that much of serum TK1 is inactive has restricted its use, particularly for solid tumors. However, all TK1 forms express the TK 210 epitope.

The path form biomarker discovery to conversion to a clinically useful companion diagnostic test presents many challenges. The talk will outline the regulatory requirements to developing a successful companion diagnostic test and the challenges that are encountered during the process. 

One-third of FDA-approved drugs target G protein-coupled receptors (GPCRs), transmembrane cell surface proteins that recognize small molecules and polypeptides with diverse chemical scaffolds.  When a drug binds to the GPCR extracellular cavity, the information is communicated over 30 Ŭ¬¬ through the plasma membrane to the receptor intracellular surface, inducing changes in the receptor structure that enable complex formation with intracellular partner proteins.  Over the past decade, x-ray crystallography has revealed the three-dimensional structures and binding modes of a growing number of unique GPCR-ligand complexes.  To better understand mechanisms of GPCR activation, this information must be complemented by knowledge of dynamic signaling pathways connecting drug-binding sites to the intracellular surface.  Here we present the development of novel approaches that reveal GPCR signaling pathways with nuclear magnetic resonance (NMR) spectroscopy in solution.  Specific applications of this approach are described for the human A2A adenosine receptor (A2AAR), where NMR uncovers the role of a key allosteric center in drug-induced signal transduction.  Finally, I will discuss the potential extension of these findings and of the presented methods toward studies of other human GPCRs.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG Binding Protein 2 (MECP2) gene. In mouse models of RTT, deficits in long-term potentiation (LTP) at Schaffer collateral (SC)-CA1 synapses in the hippocampus, as well as impairments in learning and memory. The metabotropic glutamate receptor 7 (mGlu7) is the primary mGlu receptor expressed presynaptically at SC-CA1 synapses in adult mice, and is required for the induction of LTP. By examining autopsy samples from human RTT patients, we have found an approximately 70 percent reduction in mGlu7 protein expression in both cortex and cerebellum. mGlu7 levels are also reduced in RTT model mice and positive allosteric modulation of mGlu7 activity restores LTP and improves contextual fear learning and social phenotypes. Furthermore, mGlu7 potentiation decreases apneas in RTT model mice, suggesting that mGlu7 may represent a therapeutic target for multiple aspects of the RTT phenotype.

While RTT is caused by loss-of-function mutations in MECP2, MECP2 Duplication syndrome (MDS) is another severe neurodevelopmental disorder resulting from overexpression of the MeCP2 protein. Mouse models of RTT and MDS show opposing changes in presynaptic activity at SC-CA1 synapses, and we hypothesized that genetic reduction of mGlu7 or an mGlu7 negative allosteric modulator (NAM) might correct deficits in MDS-model mice. Surprisingly, cognitive and anxiety phenotypes found in MDS animals were not impacted by reducing mGlu7 expression or by administration of an mGlu7 NAM. In contrast, a PAM unexpectedly corrected these deficits, suggesting that shared underlying circuitry changes between RTT and MDS may explain these findings. Finally, this presentation will touch upon primary GRM7 mutations and SNPs that are now being correlated with severe neurodevelopmental disorders in clinical populations.

Rapid, accurate estimation of relative ligand affinities offers the potential to allow computational methods to direct drug design and development.  Towards this goal we have developed two methods based on pre-computed ensembles; Site Identification by Ligand Competitive Saturation (SILCS) and Single-Step Free Energy Perturbation (SSFEP).  SILCS is based on computational functional group affinity mapping (FragMaps) of proteins using oscillating μex Grand Canonical Monte Carlo/Molecular Dynamics (GCMC/MD) simulations that take into account contributions from protein desolvation, functional group desolvation, protein flexibility as well as functional group-protein interactions.  The method can be applied to a range of macromolecules including those with deep or full inaccessible binding pockets such GPCRs and nuclear receptors. Grid Free Energy (GFE) FragMaps obtained from the GCMC/MD simulations may be used both qualitatively and quantitatively to direct ligand design.  In SSFEP a lead compound-protein complex is subjected to MD simulations from which an ensemble of ligand-protein conformations is obtained.  Similar calculations are done on the ligand in solution.  Free energy differences associated with small chemical modifications of the lead compound may then be evaluated using the free energy perturbation formulation in the context of single step perturbations. Both SILCS and SSFEP allow for rapid scoring of 1000s of transformations on a daily time frame offering the potential to identify synthetically accessible ligands thereby facilitating decisions concerning compounds for synthesis and testing. An overview of the SSFEP and SILCS methodologies will be presented along with application of the methods in the context of lead compound identification and optimization in the context of GPCRs. 

G-protein coupled receptors (GPCRs) represent the single largest class of druggable targets in the human genome. Of the 390 or so druggable and non-olfactory human GPCRs there exist many which are orphan and/or understudied; we refer to these as "oGPCRs". In this talk I will show how new technologies developed by my lab can illuminate the pharmacology, signaling pathways, chemical biology, distribution and function of GPCrs. I will highlight our new open-source tools which include  open-access repositories of chemical probe molecules, reporter plasmids and engineered animals that enable investigators to interrogate the biological functions of GPCRs. Given the central importance of GPCRs for all areas of biomedical research, illuminating the pharmacology, function, signaling and chemical biology of known GPCRs and oGPCRs will have far-reaching impact for both therapeutics and basic biomedical science.

Structure based drug design is now well established as a highly efficient approach in pharmaceutical research.  The approach uses atomic level detail structures of target proteins, most generally determined through X-ray crystallography. For many years this approach has not been possible for the most common classes of drug targets, particularly membrane bound proteins such as GPCRs and transporters. Approximately 10 years ago, the first X-ray structures in these areas started to emerge and the determination of more structures has begun to accelerate in the recent past. These structures cover a rapidly increasing number of targets and categories including class A, B, C and F GPCRs, endogenous amine transporters. Included in these reports are proteins in various states, novel sites for ligand modulation and other characterizations. These reports have provided valuable information facilitating the design of new compounds with specific features such as intrinsic activity (from active to inactive), ligand bias, selectivity, allosterism and others. This growing body of information will be illustrated along with examples of successes and emerging new opportunities.

GPCRs constitute the largest receptor family in the human genome. Over the years they have proven themselves to be druggable targets accounting for about 1/3 of all drugs on the market today.  Of these, approximately 15% have been approved by the US Food and Drug Administration (FDA) in the last 5 years.  Recent GPCR drug discovery efforts are expanding the range of disease indications to include polycystic ovarian syndrome, gastroparesis, pulmonary fibrosis, and smoking cessation. This talk will cover some of the novel targets, such as the calcitonin gene-related peptide (CGRP) receptor, the bile acid receptor GPBAR, the hydroxycarboxylic acid (HCA2 and HCA3) receptors, and orphan GPCRs such as GPR119.  Also covered will be the development of antibody-based therapeutics for GPCRs such as mogamulizumab for the chemokine receptor CCR4. 

Therapies that activate the host immune system have shown tremendous promise for a wide variety of solid tumors. However, in most cancer types, fewer than half of patients respond to these therapies. Epigenetic therapy can increase immune signaling from tumors, sensitizing to immune therapy in mouse models of cancer. DNA methyltransferase inhibitors (DNMTis) upregulate interferon signaling in solid tumors by cytosolic sensing of double-stranded RNA (dsRNA), triggering a Type I Interferon response and apoptosis. Demethylation and expression of bidirectionally transcribed endogenous retroviruses (ERVs) is a major component of the dsRNA that activates the response. Adding histone deacetylase inhibitors (HDACis) to DNMTis can augment this upregulation. In mouse models of cancer, DNMTi stimulate the interferon response through ERV upregulation, leading to  increased recruitment of T cells, including tumor-killing T Effector (CD3+CD8+) cells, to the tumor. This epigenetic therapy causes increased activation of CD8 T cells and natural killer cells, an increase in helper T cells, and a reduction in suppressive myeloid cells. Both the immune cell activation and the tumor burden decrease by DNMTi are dependent on activation of the Type I Interferon response and are associated with an increase in transcription of mouse ERVs. Treatment of this mouse model with the above drug combination plus anti-PD-1 significantly reduces tumor burden and increases survival. Separately, EZH2 inhibitors can increase signaling from tumor cells to recruit immune cells to kill tumors. Lastly, DNMTis can directly affect methylation on T cells to reverse T cell exhaustion. This presentation will cover work from our group and others on the use of epigenetic therapies to reverse immune evasion in cancers. 

In the last years a number of advanced nanotechnologies have been proposed developed for the  administration of drugs (nanomedicines for drug delivery), in order to provide possibilities to control their release rate, as well as their bio-distribution, and additionally preserve their stability. Between the various types of nano-medicines for drug delivery, our laboratory has expertise in the design and development of liposomal formulations, which have the advantage of being composed of completely biocompatible ingredients between others. 

Heart failure (HF) is a major problem for our contemporary societies in terms of prevalence, mortality and cost. Natriuretic peptides are recognized biomarkers for the diagnosis of HF but also for risk stratification. Innovative biomarkers are studied to improve the sub-phenotyping of HF, to facilitate the diagnosis of HF with preserved ejection fraction, and to tailor therapeutic approaches. The soluble receptor of interleukin 33 (sST2) is one of these new biomarkers. In groups of patients at higher risk of HF (hypertension, diabetes), measurement of sST2 could identify patients requiring more sustained management. In the case of HF with reduced ejection fraction, sST2 would be a powerful marker for risk estimation but also to confirm treatment choice. In the case of HF with preserved ejection fraction, measurement of sST2 may be useful for confirming a diagnosis but also for the risk stratification of the patients and as companion marker for the treatment. Interestingly, the determination of the concentrations of sST2 is facilitated by the evolution of assays with new point of care testing methods. As for many innovative biomarkers, the transition of sS2T to routine testing requires strong multidiscilplinary exchanges with physicians.

Preterm birth (PTB) is the leading cause of infant mortality and morbidity worldwide. Both preterm labor and neonatal injuries have been linked to inflammation. Of all mediators of inflammation, the major pro-inflammatory cytokine IL-1ß has been shown to trigger a specific pattern of gene expression in uterus and placenta resulting in PTB and in neonatal organ injury and significant fetal demise. Here, we show that a small peptide noncompetitive IL-1R antagonist (rytvela, labeled 101.10) designed and characterized by us, exerts potential therapeutic efficacy in preventing PTB and improving neonatal outcome. Effects of 101.10 were compared to a clinically available IL-1R competitive antagonist (Kineret). Our results show that 101.10 selectively inhibits the downstream stress-associated factors JNK, p38 and c-jun and the small GTPase Rho in myometrial smooth muscle cells and uterine explants and desirably does not interfere with the transcription factor NF-kB activity. Administration of 101.10 to pregnant mice revealed efficacy in preventing IL-1ß-, LTA- and LPS-induced PTB by down-regulating a series of proinflammatory mediators in uterus, placenta, fetal membranes, maternal circulating white blood cells and amniotic fluids. In pregnant mice treated with IL-1ß, 101.10 increased neonatal survival, and this was associated later in life with improved tissue (lung, intestine and brain) analyzed by histology. Specifically, 101.10 protected against IL-1ß-induced cerebral microvascular degeneration, loss in brain mass, which resulted in improved amplitude and latency of visual evoked potential, suggesting normalized brain function reflected in preservation of synaptic transmission through the brain of pups. In LPS-induced PTB (which mimic a gram – infection during pregnancy), 101.10 also increased neonatal survival in addition to decreasing the expression of proinflammatory mRNA transcripts in brain. 101.10 conveyed superior or comparable efficacy to Kineret in all assays performed; Kineret was largely ineffective at prolonging preterm gestation or improving neonatal outcomes, as already reported by other groups. In summary, our data describe a new potential therapeutic candidate that selectively modulates IL-1R-related signaling (thereby preserving NF-?B activity) which is effective in preventing the onset of PTB and associated adverse neonatal outcomes.

There is an acute shortage of organs due to disease, trauma, congenital defects, and most importantly, age related maladies. The synthetic materials used in tissue engineering applications today are typically composed of millimeter or micron sized particles and/or fiber dimensions. Although human cells are on the micron scale, their individual components, e.g. proteins, are composed of nanometer features. By modifying only the nanofeatures on material surfaces without changing surface chemistry, it is possible to increase tissue growth of any human tissue by controlling the endogenous adsorption of adhesive proteins onto the material surface. In addition, our group has shown that these same nanofeatures and nano-modifications can reduce bacterial growth without using antibiotics, which may further accelerate the growth of antibiotic resistant microbes. Inflammation can also be decreased through the use of nanomaterials. Finally, nanomedicine has been shown to stimulate the growth and differentiation of stem cells, which may someday be used to treat incurable disorders, such as neural damage.  This strategy also accelerates FDA approval and commercialization efforts since new chemistries are not proposed, rather chemistries already approved by the FDA with altered nanoscale features. This invited talk will highlight some of the advancements and emphasize current nanomaterials approved by the FDA for human implantation.