Integrative Biology Commons^™

Rest Upregulates Gremlin To Modulate Diffuse Intrinsic Pontine Glioma Vasculature, Shavali Shaik, Bridget Kennis, Shinji Maegawa, Keri Schadler, Yang Yanwen, Javad Nazarian, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive glial tumor that occurs in children. The extremely poor median and 5-year survival in children afflicted with DIPG highlights the need for novel biology-driven therapeutics. Here, we have implicated the chromatin remodeler and regulator of brain development called RE1 Silencing Transcription Factor (REST), in DIPG pathology. We show that REST protein is aberrantly elevated in at least 21% of DIPG tumors compared to normal controls. Its knockdown in DIPG cell lines diminished cell growth and decreased their tumorigenicity in mouse intracranial models. DIPGs are vascularized tumors and interestingly, REST loss in …

Charecterization Of The Innate Immune Response In The Rat Intervertebral Disc At The Tissue And Cellular Level, Matthew Guerreiro

Theses and Dissertations (Comprehensive)

Low back pain (LBP) affects up to 80% of the global population at some point during their life. The costs associated with LBP are estimated at $100 billion per year, putting significant strains on our healthcare system. As intervertebral disc (IVD) herniation is one of the major causes of LBP we decided to focus on herniation facilitated inflammatory responses, where damage caused by herniation triggers an innate immune response which likely results in pain, inflammation, and recruitment of specialized innate immune cells like macrophages to the affected area. Since the role of the inflammatory response is relatively uncharacterized in the …

Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie

Theses and Dissertations

Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …

Crispr Genetic Editing: Paths For Christian Acceptance And Analysis Of In Vivo And In Vitro Efficiency, Mandeep Sandhu

Scripps Senior Theses

With advancements in CRISPR-cas9 broadening the potential paths for clinical usage of genetic editing, conversations about genetic editing have grown to outside simply scientific communities and into mainstream conversations. This study focuses specifically on Christian discourse of genetic editing and locates four major tensions for many Christians when they think about genetic editing: beginning of life, Creator-human relationship, imago Dei, and stewardship. With these major concerns in mind, I identify epigenetics, somatic cell genetic editing, and in vivo genetic editing research as important research paths to pursue as they can potentially produce techniques that more Christian individuals would feel comfortable …

24-Month Hiv-Free Survival Among Infants Born To Hiv-Positive Women Enrolled In Option B+ Program In Kigali, Rwanda: The Kabeho Study, Michelle Gill, Heather J. Hoffman, Dieudonne Ndatimana, Placidie Mugwaneza, Laura Guay, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women (“Option B+”) has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother–child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 …

Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon

Dissertations and Theses (Open Access)

Salt inducible kinase 1 (SIK1) has been considered a stress-inducible kinase since it was first cloned in 1999. Continued efforts since this time have been dedicated to characterizing the structure and function of SIK1. Such research has laid the ground work for our understanding of SIK1 action and regulation in tissue and stimuli dependent manners. The fundamental findings of this dissertation continue in this tradition and include investigations of SIK1 regulatory mechanisms in skeletal muscle cells, the cellular and physiological effects of SIK1 loss of function in vitro and in vivo, and intracellular metabolic and mitochondrial regulation by this …

The Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Rs4340 Associates With Habitual Physical Activity Among European American Adults., Michael Bruneau, Theodore J Angelopoulos, Paul Gordon, Niall Moyna, Paul Visich, Robert Zoeller, Rick Seip, Stephen Bilbie, Paul Thompson, Joseph Devaney, Heather Gordish-Dressman, Eric Hoffman, Linda S Pescatello

Genomics and Precision Medicine Faculty Publications

BACKGROUND: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4340) (ACE DIP) accounts for half of the variability in plasma ACE concentrations. ACE has been widely studied for its influence on sports performance; however, research on its influence in physical activity is limited and inconsistent. We examined the influence of the ACE DIP on physical activity among 461 European Americans.

METHODS: Subjects completed the Paffenbarger Physical Activity Questionnaire for weekly walking distance. Multivariate analysis of covariance (MANCOVA) tested log-transformed differences in weekly walking distance among ACE DIP genotypes (II, ID, DD) with gender as a fixed factor, and age and body …

Walking As Ontological Shifter: Thoughts In The Key Of Life, Bibi (Silvina) Calderaro

Dissertations, Theses, and Capstone Projects

With walking as ontological shifter I pursue an alternative to the dominant modernist episteme that offers either/or onto-epistemologies of opposition and their reifying engagements. I propose this type of walking is an intentional turning towards a set of radical positions that, as integrative aesthetic and therapeutic practice, brings multiplicity and synchronicity to experience and being in an expanded sociality. This practice facilitates the conditions of possibility for recurring points of contact between the interiority perceived as ‘body’ and the exteriority perceived as ‘world.’ While making evident the self’s at once incoherence with it-self, it opens to a space beyond the …

African-American Esophageal Squamous Cell Carcinoma Expression Profile Reveals Dysregulation Of Stress Response And Detox Networks., Hayriye Verda Erkizan, Kory Johnson, Svetlana Ghimbovschi, Deepa Karkera, Gregory Trachiotis, Houtan Adib, Eric P Hoffman, Robert G Wadleigh

Genomics and Precision Medicine Faculty Publications

BACKGROUND: Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups.

METHODS: To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues.

RESULTS: …

Trap-Neuter-Return Programs And The Importance Of Associated Public Awareness, Nicolette Sliwa

Biology: Student Scholarship & Creative Works

The focus of this paper is to describe a typical Trap-Neuter-Return (TNR) program and highlight the major pros and cons surrounding this somewhat controversial method of managing the overwhelming free-roaming cat population. The effects of the species’ overabundance on the environment and human health are also discussed. Citing studies completed on TNR programs around the globe as well as mathematical models, the effectiveness of this method is compared to other, currently used alternatives. Finally, it has been suggested that the general awareness level a neighborhood possesses about the true goals of TNR programs has a potentially significant impact on the …

Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van Der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal

Genomics and Precision Medicine Faculty Publications

Dystrophin deficiency is the genetic basis for Duchenne muscular dystrophy (DMD), but the cellular basis of progressive myofiber death in DMD is not fully understood. Using two dystrophin-deficient mdx mouse models, we find that the mitochondrial dysfunction is among the earliest cellular deficits of mdx muscles. Mitochondria in dystrophic myofibers also respond poorly to sarcolemmal injury. These mitochondrial deficits reduce the ability of dystrophic muscle cell membranes to repair and are associated with a compensatory increase in dysferlin-mediated membrane repair proteins. Dysferlin deficit in mdx mice further compromises myofiber cell membrane repair and enhances the muscle pathology at an asymptomatic …

Hepatocellular Cancer Genome And Transcriptome Analysis Validates Clinically Significant Mutational Signatures With The Tgf-𝛃 Pathway, Shuyun Rao, Jian Chen, Kazufumi Ohshiro, Shoujun Gu, Sobia Zaidi, Wilma S. Jogunoori, Jon White, Nagarajan Pattabiraman, Raja Mazumder, Anelia Horvath, Ray-Chang Wu, Shulin Li, Chuxia Deng, Bibhuti Mishra, Rehan Akbanni, The Tcga Cancer Network, Lopa Mishra

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Human Ipsc-Derived Cerebellar Neurons From A Patient With Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks, Sam Nayler, Joseph Powell, Darya Vanichkina, Othmar Korn, Christine Wells, Ryan J. Taft, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Ataxia-telangiectasia (A-T) is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and …

Measuring Bacterial Growth Using A 3d-Printable Spectrometer, Samuel R. Bunting

Williams Honors College, Honors Research Projects

Visible light spectroscopy is a commonly used technique for measuring the growth of bacterial cultures, and growth curves provide broadly important data. However, the equipment and resources required for these experiments has been restricted to higher education and industry due to high cost and sophistication. We have previously reported on an inexpensive, 3D-printable photospectrometer called the SpecPhone. This device utilizes an iPhone as the camera, along with several other, inexpensive additions to make a fully functional spectrometer. Here, the application of the SpecPhone is expanded to the quantification of actively dividing E. coli cultures. Two protocols have been developed; one …

Vamorolone, A Dissociative Steroidal Compound, Reduces Pro-Inflammatory Cytokine Expression In Glioma Cells And Increases Activity And Survival In A Murine Model Of Cortical Tumor., Elizabeth Wells, Madhuri Kambhampati, Jesse M Damsker, Heather Gordish-Dressman, Sridevi Yadavilli, Oren J Becher, Jamila Gittens, Mojca Stampar, Roger J. Packer, Javad Nazarian

Genomics and Precision Medicine Faculty Publications

Corticosteroids, such as dexamethasone, are routinely used as palliative care in neuro-oncology for their anti-inflammatory benefits, however many patients experience dose limiting side effects caused by glucocorticoid response element (GRE)-mediated transcription. The purpose of this study was to use a murine model to investigate a new steroid alternative, vamorolone, which promises to reduce side effects through dissociating GRE-mediated transcription and NF-κB -mediated anti-inflammatory actions. To compare vamorolone to dexamethasone in reducing pro-inflammatory signals in vitro, murine glioma cells were treated with dexamethasone, vamorolone or vehicle control. Changes in mRNA expression were assessed using the nanostring inflammatory platform. Furthermore, drug …

Effect Of Arginine On Oligomerization And Stability Of N-Acetylglutamate Synthase., N Haskins, A Mumo, P H Brown, Mendel Tuchman, Hiroki Morizono, L Caldovic

Genomics and Precision Medicine Faculty Publications

N-acetylglutamate synthase (NAGS; E.C.2.3.1.1) catalyzes the formation of N-acetylglutamate (NAG) from acetyl coenzyme A and glutamate. In microorganisms and plants, NAG is the first intermediate of the L-arginine biosynthesis; in animals, NAG is an allosteric activator of carbamylphosphate synthetase I and III. In some bacteria bifunctional N-acetylglutamate synthase-kinase (NAGS-K) catalyzes the first two steps of L-arginine biosynthesis. L-arginine inhibits NAGS in bacteria, fungi, and plants and activates NAGS in mammals. L-arginine increased thermal stability of the NAGS-K from Maricaulis maris (MmNAGS-K) while it destabilized the NAGS-K from Xanthomonas campestris (XcNAGS-K). Analytical gel chromatography and ultracentrifugation indicated tetrameric structure of the …

Zombies, Predatory Wasps And Consciousness, James K. Peterson

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Identification Of Pathway-Specific Serum Biomarkers Of Response To Glucocorticoid And Infliximab Treatment In Children With Inflammatory Bowel Disease, Christopher R. Heier, Alyson A. Fiorillo, Ellen Chaisson, Heather A. Gordish-Dressman, Yetrib Hathout, Jesse M. Damsker, Eric P. Hoffman, Laurie S. Conklin

Genomics and Precision Medicine Faculty Publications

Objective:

Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial.

Methods:

We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect. Serum was obtained from children with IBD before and after treatment with either corticosteroids (prednisone; n=12) or anti-tumor necrosis factor-α biologic (infliximab; n=7). Over 1,100 serum proteins were assayed using aptamer-based SOMAscan proteomics, and 22 miRNAs analyzed …

Optimization Of A Genomic Editing System Using Crispr/Cas9-Induced Site-Specific Gene Integration, Jillian L. Mccool Ms., Nick Hum, Gabriela G. Loots

STAR Program Research Presentations

The CRISPR-Cas system is an adaptive immune system found in bacteria which helps protect against the invasion of other microorganisms. This system induces double stranded breaks at precise genomic loci (1) in which repairs are initiated and insertions of a target are completed in the process. This mechanism can be used in eukaryotic cells in combination with sgRNAs (1) as a tool for genome editing. By using this CRISPR-Cas system, in addition to the “safe harbor locus,” ROSAβ26, the incorporation of a target gene into a site that is not susceptible to gene silencing effects can be achieved through few …

Histological And Molecular Analysis Of A Progressive Diffuse Intrinsic Pontine Glioma And Synchronous Metastatic Lesions: A Case Report., Javad Nazarian, Gary E Mason, Cheng Ying Ho, Eshini Panditharatna, Madhuri Kambhampati, Louis Gilbert Vezina, Roger J. Packer, Eugene I Hwang

Genomics and Precision Medicine Faculty Publications

There is no curative treatment for patients with diffuse intrinsic pontine glioma (DIPG). However, with the recent availability of biopsy and autopsy tissue, new data regarding the biologic behavior of this tumor have emerged, allowing greater molecular characterization and leading to investigations which may result in improved therapeutic options. Treatment strategies must address both primary disease sites as well as any metastatic deposits, which may be variably sensitive to a particular approach.In this case report, we present a patient with DIPG treated with irradiation and serial investigational agents. The clinical, pathological and molecular phenotypes of both the progressive primary tumor …

Rescuing Perishable Neuroanatomical Information From A Threatened Biodiversity Hotspot: Remote Field Methods For Brain Tissue Preservation Validated By Cytoarchitectonic Analysis, Immunohistochemistry, And X-Ray Microcomputed Tomography, Daniel Hughes, Ellen Walker, Paul Gignac, Anais Martinez, Kenichiro Negishi, Carl Lieb, Eli Greenbaum, Arshad Khan

Selected Works Temporary Series

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, areincreasingly threatened. There is a need to accelerate collection efforts in these regionsbefore threatened or endangered species become extinct. The diverse geographical, ecological,genetic, morphological, and behavioral data generated from the on-site collection ofan individual specimen are useful for many scientific purposes. However, traditional methodsfor specimen preparation in the field do not permit researchers to retrieve neuroanatomicaldata, disregarding potentially useful data for increasing our understanding of braindiversity. These data have helped clarify brain evolution, deciphered relationships betweenstructure and function, and revealed constraints and selective pressures that provide contextabout the evolution …

Rescuing Perishable Neuroanatomical Information From A Threatened Biodiversity Hotspot: Remote Field Methods For Brain Tissue Preservation Validated By Cytoarchitectonic Analysis, Immunohistochemistry, And X-Ray Microcomputed Tomography, Hughes, Ellen Walker, Paul Gignac, Anais Martinez, Kenichiro Negishi, Carl Lieb, Eli Greenbaum, Arshad Khan

Departmental Papers (Biology)

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, areincreasingly threatened. There is a need to accelerate collection efforts in these regionsbefore threatened or endangered species become extinct. The diverse geographical, ecological,genetic, morphological, and behavioral data generated from the on-site collection ofan individual specimen are useful for many scientific purposes. However, traditional methodsfor specimen preparation in the field do not permit researchers to retrieve neuroanatomicaldata, disregarding potentially useful data for increasing our understanding of braindiversity. These data have helped clarify brain evolution, deciphered relationships betweenstructure and function, and revealed constraints and selective pressures that provide contextabout the evolution …

Genomic Drivers Of Cutaneous Squamous Cell Carcinoma Development, Vida Chitsazzadeh

Dissertations and Theses (Open Access)

Skin cancer is the most common malignancy in humans. Annually, in U.S. there are over 3 million cases with an estimated overall economic impact of $2 billion. Cutaneous Squamous Cell Carcinoma (cuSCC) comprises 15-20% of all skin cancers. cuSCC has the best-defined progression from a distinct precancerous lesion, the Actinic Keratosis (AK), to invasive cuSCC. Destructive therapies for AK treatment must be used repetitively, causing significant morbidity. There is a tremendous need for targeted diagnostics and therapy for AKs, representing an important opportunity for secondary skin cancer prevention. Our knowledge of the molecular and cellular events that lead to the …

An Analysis Of Bacterial Contamination Of Chicken Eggs And Antimicrobial Resistance, Holly Spitzer

All College Thesis Program, 2016-2019

Chicken eggs are a major component of American diets, with an average yearly consumption of approximately 250 eggs per person (American Humane Society). While highly nutritious, eggs are also one of the leading causes of food poisoning and food borne illness in the United States. Eggs may become contaminated by a number of different types of bacteria during production, including Salmonella, a group of bacteria that, according to the CDC, causes more than 1.2 million cases of food borne illness in the United States every year. In an effort to decrease the frequency of bacterial contamination, many food producers …

Effect Of The Il-1 Receptor Antagonist Kineret® On Disease Phenotype In Mdx Mice., Margaret E. Benny Klimek, Arpana Sali, Sree Rayavarapu, Jack Van Der Meulen, Kanneboyina Nagaraju

Genomics and Precision Medicine Faculty Publications

Duchenne muscular dystrophy (DMD) is an X-linked muscle disease caused by mutations in the dystrophin gene. The pathology of DMD manifests in patients with progressive muscle weakness, loss of ambulation and ultimately death. One of the characteristics of DMD is muscle inflammation, and dystrophin-deficient skeletal muscles produce higher levels of the pro-inflammatory cytokine interleukin 1β (IL-1β) in response to toll like receptor (TLR) stimulation compared to controls; therefore, blocking the IL-1β pathway could improve the disease phenotype in mdx mice, a mouse model of DMD. Kineret® or IL-1Ra is a recombinant IL-1 receptor antagonist approved by the FDA for treating …

Effects On Muscle Tissue Remodeling And Lipid Metabolism In Muscle Tissue From Adult Patients With Polymyositis Or Dermatomyositis Treated With Immunosuppressive Agents., Ingela Loell, Joan Raouf, Yi-Wen Chen, Rongye Shi, Inger Nennesmo, Helene Alexanderson, Maryam Dastmalchi, Kanneboyina Nagaraju, Marina Korotkova, Ingrid E Lundberg

Genomics and Precision Medicine Faculty Publications

BACKGROUND: Polymyositis (PM) and dermatomyositis (DM) are autoimmune muscle diseases, conventionally treated with high doses of glucocorticoids in combination with immunosuppressive drugs. Treatment is often dissatisfying, with persisting muscle impairment. We aimed to investigate molecular mechanisms that might contribute to the persisting muscle impairment despite immunosuppressive treatment in adult patients with PM or DM using gene expression profiling of repeated muscle biopsies.

METHODS: Paired skeletal muscle biopsies from six newly diagnosed adult patients with DM or PM taken before and after conventional immunosuppressive treatment were examined by gene expression microarray analysis. Selected genes that displayed changes in expression were analyzed …

Factors Affecting Injury History And Their Overall Impact On Athletic Performance In Distance Runners, Trevor Norris

Williams Honors College, Honors Research Projects

Distance running is a very precise mechanism of many intricate movements and abilities of the body. The amount of miles that a distance runner must run puts a lot of very intense stresses on one’s body. These stresses often appear at the bone level and lead to many injuries such as stress reactions and stress fractures but also may play important roles in tissue damages such as strains and pulls. In this study, we used division one college distance runners and examined many intricacies between their level of fitness and overall composition. These include looking at imbalances, dominant traits, and …

Are Immune Modulating Single Nucleotide Polymorphisms Associated With Necrotizing Enterocolitis?, Ashanti L Franklin, Mariam Said, Clint D Cappiello, Heather Gordish-Dressman, Zohreh Tatari-Calderone, Stanislav Vukmanovic, Khodayar Rais-Bahrami, Naomi L C Luban, Joseph M Devaney, Anthony D Sandler

Genomics and Precision Medicine Faculty Publications

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over …

Effect Of Genetic Background On The Dystrophic Phenotype In Mdx Mice., William D Coley, Laurent Bogdanik, Maria Candida Vila, Qing Yu, Terence A Partridge, Kanneboyina Nagaraju, +12 Additional Authors

Genomics and Precision Medicine Faculty Publications

Genetic background significantly affects phenotype in multiple mouse models of human diseases, including muscular dystrophy. This phenotypic variability is partly attributed to genetic modifiers that regulate the disease process. Studies have demonstrated that introduction of the γ-sarcoglycan null allele onto the DBA/2J background confers a more severe muscular dystrophy phenotype than the original strain, demonstrating the presence of genetic modifier loci in the DBA/2J background. To characterize the phenotype of dystrophin deficiency on the DBA/2J background, we created and phenotyped DBA/2J-congenic Dmdmdx mice (D2-mdx) and compared them to the original, C57BL/10ScSn-Dmdmdx (B10-mdx) model. These strains were compared to their respective …

Bioregulatory Systems Medicine: An Innovative Approach To Integrating The Science Of Molecular Networks, Inflammation, And Systems Biology With The Patient's Autoregulatory Capacity?, Alyssa W Goldman, Yvonne Burmeister, Konstantin Cesnulevicius, Martha Herbert, Mary Kane, David Lescheid, Timothy Mccaffrey, Myron Schultz, Bernd Seilheimer, Alta Smit, Georges St Laurent, Brian Berman

Medicine Faculty Publications

Bioregulatory systems medicine (BrSM) is a paradigm that aims to advance current medical practices. The basic scientific and clinical tenets of this approach embrace an interconnected picture of human health, supported largely by recent advances in systems biology and genomics, and focus on the implications of multi-scale interconnectivity for improving therapeutic approaches to disease. This article introduces the formal incorporation of these scientific and clinical elements into a cohesive theoretical model of the BrSM approach. The authors review this integrated body of knowledge and discuss how the emergent conceptual model offers the medical field a new avenue for extending the …