Digital Commons Network^™

Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov

Chemistry & Biochemistry Faculty Publications

n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds …

Ghost Mitochondria Drive Metastasis Through Adaptive Gcn2/Akt Therapeutic Vulnerability, Jagadish C Ghosh, Michela Perego, Ekta Agarwal, Irene Bertolini, Yuan Wang, Aaron R Goldman, Hsin-Yao Tang, Andrew V Kossenkov, Catherine J Libby, Lucia R Languino, Edward F Plow, Annamaria Morotti, Luisa Ottobrini, Marco Locatelli, David W Speicher, M Cecilia Caino, Joel Cassel, Joseph M Salvino, Marie E Robert, Valentina Vaira, Dario C Altieri

Department of Cancer Biology Faculty Papers

Cancer metabolism, including in mitochondria, is a disease hallmark and therapeutic target, but its regulation is poorly understood. Here, we show that many human tumors have heterogeneous and often reduced levels of Mic60, or Mitofilin, an essential scaffold of mitochondrial structure. Despite a catastrophic collapse of mitochondrial integrity, loss of bioenergetics, and oxidative damage, tumors with Mic60 depletion slow down cell proliferation, evade cell death, and activate a nuclear gene expression program of innate immunity and cytokine/chemokine signaling. In turn, this induces epithelial-mesenchymal transition (EMT), activates tumor cell movements through exaggerated mitochondrial dynamics, and promotes metastatic dissemination in vivo. In …

Effects Of Placebo Administration On Immune Mechanisms And Relationships With Central Endogenous Opioid Neurotransmission, Alan Prossin, Alisa Koch, Phillip Campbell, Geoffroy Laumet, Christian S Stohler, Robert Dantzer, Jon-Kar Zubieta

Faculty, Staff and Student Publications

Behavioral conditioning and expectation can have profound impact on animal and human physiology. Placebo, administered under positive expectation in clinical trials, can have potent effects on disease pathology, obscuring active medications. Emerging evidence suggests placebo-responsive neurotransmitter systems (e.g., endogenous opioid) regulate immune function by manipulating inflammatory proteins including IL-18, a potent pro-inflammatory, nociceptive cytokine implicated in pathophysiology of various diseases. Validation that neuroimmune interactions involving brain μ-opioid receptor (MOR) activity and plasma IL-18 underlie placebo analgesic expectation could have widespread clinical applications. Unfortunately, current lack of mechanistic clarity obfuscates clinical translation. To elucidate neuroimmune interactions underlying placebo analgesia, we exposed …

Fbxw7-Mediated Erk3 Degradation Regulates The Proliferation Of Lung Cancer Cells, Hyun-Jung An, Cheol-Jung Lee, Ga-Eun Lee, Youngwon Choi, Dohyun Jeung, Weidong Chen, Hye Suk Lee, Han Chang Kang, Joo Young Lee, Dae Joon Kim

School of Medicine Publications

Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein kinase (MAPK) family, members of which play essential roles in diverse cellular processes during carcinogenesis, including cell proliferation, differentiation, migration, and invasion. Unlike other MAPKs, ERK3 is an unstable protein with a short half-life. Although deubiquitination of ERK3 has been suggested to regulate the activity, its ubiquitination has not been described in the literature. Here, we report that FBXW7 (F-box and WD repeat domain-containing 7) acts as a ubiquitination E3 ligase for ERK3. Mammalian two-hybrid assay and immunoprecipitation results demonstrated that ERK3 is a novel binding partner …

Phytochemical Investigation Of Egyptian Riverhemp: A Potential Source Of Antileukemic Metabolites, Shimaa M. Abdelgawad, Mona H. Hetta, Mohamed A. Ibrahim, Premalatha Balachandran

Faculty and Student Publications

As part of our research group's continuous efforts to find alternative treatments for cancer, the aqueous ethanol extract of Sesbania sesban L. Merr. (SS, Egyptian riverhemp) demonstrated an antileukemic activity against K562 cell line. Bioguided fractionation of SS leaves hydroethanolic extract resulted in the isolation of one new compound (33) named as hederatriol 3-O-β-D-glucuronic acid methyl ester as well as 34 known compounds. Seven compounds ((34), (22), (20), (24), (21), (19), and (35)) showed high antiproliferative effects (IC50 = 22.3, 30.8, 31.3, 33.7, 36.6, 37.5, and 41.5 μM, respectively), while four compounds ((32), (5), (29), and (1)) showed milder activities …

Insect Cell Expression And Purification Of Recombinant Sars-Cov-2 Spike Proteins That Demonstrate Ace2 Binding, Lucas R. Struble, Audrey L. Smith, William E. Lutz, Gabrielle Grubbs, Satish Sagar, Kenneth W. Bayles, Prakash Radhakrishnan, Surender Khurana, Dalia El-Gamal, Gloria E. O. Borgstahl

Journal Articles: Pathology and Microbiology

The COVID-19 pandemic caused by SARS-CoV-2 infection has led to socio-economic shutdowns and the loss of over 5 million lives worldwide. There is a need for the identification of therapeutic targets to treat COVID-19. SARS-CoV-2 spike is a target of interest for the development of therapeutic targets. We developed a robust SARS-CoV-2 S spike expression and purification protocol from insect cells and studied four recombinant SARS-CoV-2 spike protein constructs based on the original SARS-CoV-2 sequence using a baculovirus expression system: a spike protein receptor-binding domain that includes the SD1 domain (RBD) coupled to a fluorescent tag (S-RBD-eGFP), spike ectodomain coupled …

At-Home Blood Collection And Stabilization In High Temperature Climates Using, Lauren G Brown, Amanda J Haack, Dakota S Kennedy, Karen N Adams, Jennifer E Stolarczuk, Meg G Takezawa, Erwin Berthier, Sanitta Thongpang, Fang Yun Lim, Damien Chaussabel, Mathieu Garand, Ashleigh B Theberge

Faculty Research 2022

Expanding whole blood sample collection for transcriptome analysis beyond traditional phlebotomy clinics will open new frontiers for remote immune research and telemedicine. Determining the stability of RNA in blood samples exposed to high ambient temperatures (>30°C) is necessary for deploying home-sampling in settings with elevated temperatures (e.g., studying physiological response to natural disasters that occur in warm locations or in the summer). Recently, we have developed

The Imaginal Lexicon Of Aging Studies, William Ebenstein

Publications and Research

Aging Studies focuses on the cultural, humanistic and experiential aspects of aging insofar as these are already embedded in literature, art, language and everyday life. The lexicon of this multi-disciplinary field has evolved in response to shifts in cultural attitudes, social roles, and conceptual frameworks. At the same time, many age-related words have links to poetic imagery and ancient myths, and to evocative etymologies that conjure an historical context. The article looks at the ongoing and surprisingly difficult effort to find the right word to call an older person. It reviews the language and literary genres associated with longevity. And, …

Transcranial Magnetic Stimulation For Post-Traumatic Stress Disorder, Amber N. Edinoff, Tanner L. Hegefeld, Murray Petersen, James C. Patterson, Christopher Yossi, Jacob Slizewski, Ashley Osumi, Elyse M. Cornett, Adam M. Kaye, Jessica S. Kaye, Vijayakumar Javalkar, Omar Viswanath, Ivan Urits, Alan David Kaye

School of Pharmacy Faculty Articles

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that causes significant functional impairment and is related to altered stress response and reinforced learned fear behavior. PTSD has been found to impact three functional networks in the brain: default mode, executive control, and salience. The executive control network includes the dorsolateral prefrontal cortex (DLPFC) and lateral PPC. The salience network involves the anterior cingulate cortex, anterior insula, and amygdala. This latter network has been found to have increased functional connectivity in PTSD. Transcranial Magnetic Stimulation (TMS) is a technique used in treating PTSD and involves stimulating specific portions of the brain …

Analysis Of Hematocrit Levels In Walleye Sander Vitreus From Similar Waterbodies, Alyssa Hauser

Journal of Earth and Life Science

Walleye Sander vitreus are a popular fish among anglers and hold a prominent place in Minnesotan’s identity as their state fish. Because of this, multiple management practices are used to ensure the continued health of their populations within Minnesota waters. In this study, the process of analyzing hematocrit levels was used to determine if the analysis of hematological parameters could be a useful tool in detecting differences in population health. To evaluate this, blood samples were acquired from age-0 and age-1 fish from two similar lakes and run through a hematocrit centrifuge to separate platelets from plasma to read the …

Development Of Zafirlukast Derivatives Active Against Porphyromonas Gingivalis, Kaitlind C. Howard

Theses and Dissertations--Pharmacy

Periodontal diseases are inflammatory diseases that can lead to damage of the soft tissue and bone supporting the teeth. Gingivitis is the reversible early stage of gum disease, which consist of gums that bleed when brushing or flossing teeth. When left untreated, the preventable but irreversible late stage of periodontal disease, periodontitis, can lead teeth to loosen or even fall out. Oral bacterial species, such as the Gram-negative anaerobic pathogen Porphyromonas gingivalis trigger these inflammatory diseases through oral dysbiosis. P. gingivalis is a keystone pathogen, meaning that the damage caused by P. gingivalis is not proportional to its abundance. Treatment …

Capture-Recapture Reveals Heterogeneity In Habitat-Specific Mongoose Densities And Spatiotemporal Variability In Trapping Success In St. Kitts, West Indies, Caroline C. Sauvé, Are R. Berentsen, Amy Gilbert, Anne Conan, Luis Cruz-Martinez, Patrick A. Leighton

United States Department of Agriculture Wildlife Services: Staff Publications

The small Indian mongoose (Urva auropunctata) is a non-native invasive species across the Caribbean and a rabies reservoir on at least four islands in the region. Although previous studies reported mongoose density estimates in their non-native range, the variability in trapping designs, study seasonality, and analytical methods among studies precludes direct comparisons. This study is the first to report mongoose densities for the island of St. Kitts, West Indies. Our objective was to quantify mongoose densities across four habitats characteristic for the island. High capture and recapture rates in this study resulted in detailed estimates of spatial heterogeneity …

Design And Synthesis Of Curcumin Analogs For Anticancer Activity And Discovery Of Novel Hit Molecules Targeting Cxcr4., Maryam Sadat Hosseini Zare

Dissertations (2016-Present)

Curcumin as a natural compound is made of various components including protein, carbohydrate, and curcuminoid. Curcuminoid is made of curcumin, desmethoxycurcumin and bis desmethoxycurcumin. Curcumin is used for the treatment of cancer and inflammatory disorders, but it has some therapeutic problems like poor bioavailability, poor efficacy, and chemical instability. To overcome these problems, the objective of this study is (1) synthesis of pyrazole curcumin analogs, (2) synthesis of triazole curcumin analogs, and (3) in-vitro study of the anticancer activity of these curcumin analogs on head & neck, breast, pancreatic and glioblastoma cancer cells. During this part of my Ph.D. project, …

Comparative Analysis Of Gene Expression Patterns For Oral Epithelial Cell Functions In Periodontitis, Octavio A Gonzalez, Sreenatha Kirakodu, Linh M Nguyen, Luis Orraca, Michael J Novak, Janis Gonzalez-Martinez, Jeffrey L Ebersole

Faculty, Staff and Student Publications

The structure and function of epithelial cells are critical for the construction and maintenance of intact epithelial surfaces throughout the body. Beyond the mechanical barrier functions, epithelial cells have been identified as active participants in providing warning signals to the host immune and inflammatory cells and in communicating various detailed information on the noxious challenge to help drive specificity in the characteristics of the host response related to health or pathologic inflammation. Rhesus monkeys were used in these studies to evaluate the gingival transcriptome for naturally occurring disease samples (GeneChip® Rhesus Macaque Genome Array) or for ligature-induced disease (GeneChip® Rhesus …

Completing Single-Cell Dna Methylome Profiles Via Transfer Learning Together With Kl-Divergence, Sanjeeva Dodlapati, Zongliang Jiang, Jiangwen Sun

Computer Science Faculty Publications

The high level of sparsity in methylome profiles obtained using whole-genome bisulfite sequencing in the case of low biological material amount limits its value in the study of systems in which large samples are difficult to assemble, such as mammalian preimplantation embryonic development. The recently developed computational methods for addressing the sparsity by imputing missing have their limits when the required minimum data coverage or profiles of the same tissue in other modalities are not available. In this study, we explored the use of transfer learning together with Kullback-Leibler (KL) divergence to train predictive models for completing methylome profiles with …

Morphological Description Of Laevicaulisstuhlmanni (Simroth, 1895) (Pulmonata, Veronicellidae) From Egypt, Reham Fathey Ali, David G Robinson, Fabio Liberto

Faculty, Staff and Student Publications

BACKGROUND: Terrestrial slugs and snails are increasingly becoming serious pests of agricultural, horticultural and ornamental plants in Egypt, resulting in major economic losses.

NEW INFORMATION: This paper provides a detailed morphological and anatomical description of the veronicellid slug Laevicaulisstuhlmanni (Simroth, 1895) that has been recently recorded from Egypt. This population from Egypt is compared with Laevicaulis populations recently reported and described from Libya as L.striatus (Simroth, 1896) and with available data in literature. Some notes and a distribution map of the veronicellids introduced in north-eastern Africa are provided.

Comparison Of M, Mm And Lts Estimators In Linear Regression In The Presence Of Outlier, Cem Tirink, Hasan Önder

Turkish Journal of Veterinary & Animal Sciences

In this study, it was aimed to evaluate the performance of different estimators that will be used in regression analysis, which is one of the multivariate statistical methods in the presence of outliers in the data set. Sixth month live weight was estimated with various body measurements for Saanen kids taken from a private farm. In the data set, the use and performance of robust estimators were evaluated because the least squares method did not provide reliable results in the case of outliers. M (for Huber and Tukey bisquare) estimator, MM estimator and LTS estimator were used as robust used …

Determination Of Acrylamide Using The Immuno-Enzymatic Method In Commercial Dog And Cat Foods, Ni̇met Kiliç, Bi̇lal Cem Li̇man

Turkish Journal of Veterinary & Animal Sciences

Pet animals raised by humans do not have the chance to choose their own food. Therefore, mistakes made by humans in feeding dogs and cats will adversely affect the health of the animal. There are applications at high temperatures at various stages during the production of dog and cat foods. It is predicted that acrylamide (AA) can be formed as a result of a possible Maillard reaction since the cat and dog foods contain starch in its structure. The aim of this study is to determine the AA residue immuno-enzymatically in dry cat and dog feeds from different companies available …

Malaria Resilience In South America: Epidemiology, Vector Biology, And Immunology Insights From The Amazonian International Center Of Excellence In Malaria Research Network In Peru And Brazil, Kathrine Torres, Marcelo U. Ferreira, Marcia C. Castro, Ananias A. Escalante, Jan E. Conn, Elizabeth Villasis, Maisa Da Silva Araujo, Gregorio Almeida, Priscila T. Rodrigues, Rodrigo M. Corder, Anderson R.J. Fernandes, Priscila R. Calil, Winni A. Ladeia, Stefano S. Garcia-Castillo, Joaquin Gomez, Lis Ribeiro Do Valle Antonelli, Ricardo T. Gazzinelli, Douglas T. Golenbock, Alejandro Llanos-Cuentas, Dionicia Gamboa, Joseph M. Vinetz

Harold W. Manter Laboratory of Parasitology: Library Materials

The 1990s saw the rapid reemergence of malaria in Amazonia, where it remains an important public health priority in South America. The Amazonian International Center of Excellence in Malaria Research (ICEMR) was designed to take a multidisciplinary approach toward identifying novel malaria control and elimination strategies. Based on geographically and epidemiologically distinct sites in the Northeastern Peruvian and Western Brazilian Amazon regions, synergistic projects integrate malaria epidemiology, vector biology, and immunology. The Amazonian ICEMR’s overarching goal is to understand how human behavior and other sociodemographic features of human reservoirs of transmission— predominantly asymptomatically parasitemic people—interact with the major Amazonian malaria …

At-Home Blood Collection And Stabilization In High Temperature Climates Using Home Rna, Lauren G Brown, Amanda J Haack, Dakota S Kennedy, Karen N Adams, Jennifer E Stolarczuk, Meg G Takezawa, Erwin Berthier, Sanitta Thongpang, Fang Yun Lim, Damien Chaussabel, Mathieu Garand, Ashleigh B Theberge

2020-Current year OA Pubs

Expanding whole blood sample collection for transcriptome analysis beyond traditional phlebotomy clinics will open new frontiers for remote immune research and telemedicine. Determining the stability of RNA in blood samples exposed to high ambient temperatures (>30°C) is necessary for deploying home-sampling in settings with elevated temperatures (e.g., studying physiological response to natural disasters that occur in warm locations or in the summer). Recently, we have developed

Conserving Endangered Black-Footed Ferrets: Biological Threats, Political Challenges, And Lessons Learned, Travis M. Livieri, Steven C. Forrest, Marc R. Matchett, Stewart Breck

United States Department of Agriculture Wildlife Services: Staff Publications

There may be few stories in the annals of wildlife management that are as dramatic as the near demise and comeback of the black-footed ferret (Mustela nigripes). Endemic only to North America, this charming little carnivore found only in the continent’s central grasslands was hardly known to science until the mid-20th century. By then, vast colonies of the prey it depended on for food and shelter, the prairie dog (Cynomys spp.), had been wiped out through disease (sylvatic plague) and an agricultural industry with little tolerance for burrowing and grazing rodents. At its low point, the species’ …

Prefrontal Glutamate Neurotransmission In Ptsd: A Novel Approach To Estimate Synaptic Strength In Vivo In Humans, Lynnette A Averill, Lihong Jiang, Prerana Purohit, Anastasia Coppoli, Christopher L Averill, Jeremy Roscoe, Benjamin Kelmendi, Henk M De Feyter, Robin A De Graaf, Ralitza Gueorguieva, Gerard Sanacora, John H Krystal, Douglas L Rothman, Graeme F Mason, Chadi G Abdallah

Staff and Researcher Publications

Background: Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in vivo in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic strength, termed energy-per-cycle (EPC). Then, we used EPC to investigate the role of prefrontal neurotransmission in trauma-related psychopathology.

Methods: Healthy controls (n = 18) and patients with posttraumatic stress (PTSD; n = 16) completed 13C-acetate magnetic resonance spectroscopy (MRS) scans to estimate prefrontal EPC, which is the ratio of neuronal energetic needs per glutamate neurotransmission cycle (VTCA/VCycle).

Results: Patients …

Lipid A-Ara4n As An Alternate Pathway For (Colistin) Resistance In Klebsiella Pneumonia Isolates In Pakistan, Kiran I. Masood, Seema Umar, Zahra Hasan, Joveria Farooqi, Safina Abdul Razzak, Nazish Jabeen, Jason Rao Jason Rao, Sadia Shakoor, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objectives: This study aimed to explore mechanism of colistin resistance amongst Klebsiella pneumoniae isolates through plasmid mediated mcr-1 gene in Pakistan. Carbapenem and Colistin resistant K. pneumoniae isolates (n = 34) stored at - 80 °C as part of the Aga Khan University Clinical Laboratory strain bank were randomly selected and subjected to mcr-1 gene PCR. To investigate mechanisms of resistance, other than plasmid mediated mcr-1 gene, whole genome sequencing was performed on 8 clinical isolates, including 6 with colistin resistance (MIC > 4 μg/ml) and 2 with intermediate resistance to colistin (MIC > 2 μg/ml).
Results: RT-PCR conducted revealed absence of …

Medical School Watercooler Newsletter - November 5, 2021, Lindsey Lyle

Watercooler Newsletter

This is the November 5, 2021 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents include:

• Video online: 'Emerging Trends in Radiation for Breast Cancer'
• Williams presents on COVID-19 vaccine hesitancy at national meeting
• Estrada recognized by Sun Belt Conference for pandemic collaboration
• Mitchell Cancer Institute's colon cancer research featured in national journal
• Faculty Spotlight: Daniel McMahon, M.D.
• Carpenter recognized for top academic performance
• Trauma surgeon and youth advocate joins surgery faculty
• Thakur to discuss 'Skull Base Neurosurgery and Brain Tumors' at Med School Café
• Meet a Med Student: Lita Araysi
• Basic Medical Sciences Graduate Program …

A Human Ipsc-Derived Inducible Neuronal Model Of Niemann-Pick Disease, Type C1, Anika V Prabhu, Insung Kang, Raffaella De Pace, Christopher A Wassif, Hideji Fujiwara, Pamela Kell, Xuntian Jiang, Daniel S Ory, Juan S Bonifacino, Michael E Ward, Forbes D Porter

2020-Current year OA Pubs

BACKGROUND: Niemann-Pick disease, type C (NPC) is a childhood-onset, lethal, neurodegenerative disorder caused by autosomal recessive mutations in the genes NPC1 or NPC2 and characterized by impaired cholesterol homeostasis, a lipid essential for cellular function. Cellular cholesterol levels are tightly regulated, and mutations in either NPC1 or NPC2 lead to deficient transport and accumulation of unesterified cholesterol in the late endosome/lysosome compartment, and progressive neurodegeneration in affected individuals. Previous cell-based studies to understand the NPC cellular pathophysiology and screen for therapeutic agents have mainly used patient fibroblasts. However, these do not allow modeling the neurodegenerative aspect of NPC disease, highlighting …

A Southwestern United States Pilot Investigation Of Triatomine–Mite Prevalence, Kyndall C. Dye-Braumuller, Hanna Waltz, Mary K. Lynn, Stephen A. Klotz, Justin O. Schmidt, Alvaro Romero, Marvin Stanley Rodriguez Aquino, Jose Ricardo Palacios Valladares, Pamela Michelle Cornejo Rivas, Melissa Nolan Ph.D., Mph

Faculty Publications

An estimated 70 million persons in the Western Hemisphere are living at risk for Chagas disease, a parasitic infection transmitted to humans by over 156 different competent triatomine insect vector species. Prior Pan American Health Organization insecticide campaigns throughout Latin America in the 1990s and 2000s demonstrated that domestic insecticide spraying had temporary effects, which resulted in the re-establishment of triatomine species within a few years. Serendipitously, our team found ectoparasitic mites parasitizing triatomines collected from the field in multiple locations in the southwestern United States, where human–triatomine interaction was high but human parasite infection remains low. Upon further investigation …

Activity-Dependent Modulation Of Synapse-Regulating Genes In Astrocytes, Isabella Farhy-Tselnicker, Matthew M Boisvert, Hanqing Liu, Cari Dowling, Galina A Erikson, Elena Blanco-Suarez, Chen Farhy, Maxim N Shokhirev, Joseph R Ecker, Nicola J Allen

Department of Neurosurgery Faculty Papers

Astrocytes regulate the formation and function of neuronal synapses via multiple signals, however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually-evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development are also altered when astrocyte signaling is blunted by diminishing calcium release from …

Artificial Intelligence Toward Personalized Medicine, Muhammad Wildan Gifari, Pugud Samodro, Dhadhang Wahyu Kurniawan

Pharmaceutical Sciences and Research

In current medical practice when a patient feels symptoms he/she would consult the doctor. The doctor then gives medication in a one-fits-all fashion. However, recent genetics studies had shown that different genetic makeup can results in different effects on medication, so the medication should be customed for every individual. The main idea of “personalized medicine” is to provide the right intervention including medication to the right patient at the right time and dose. With this approach, the medication paradigm would shift from curative to preventive. The rise of personalized medicine had been possible because the information from ever-increasing biomolecular (proteomics, …

From Mathematics To Medicine: A Practical Primer On Topological Data Analysis (Tda) And The Development Of Related Analytic Tools For The Functional Discovery Of Latent Structure In Fmri Data, Andrew Salch, Adam Regalski, Hassan Abdallah, Raviteja Suryadevara, Michael J. Catanzaro, Vaibhav A. Diwadkar

Mathematics Faculty Research Publications

fMRI is the preeminent method for collecting signals from the human brain in vivo, for using these signals in the service of functional discovery, and relating these discoveries to anatomical structure. Numerous computational and mathematical techniques have been deployed to extract information from the fMRI signal. Yet, the application of Topological Data Analyses (TDA) remain limited to certain sub-areas such as connectomics (that is, with summarized versions of fMRI data). While connectomics is a natural and important area of application of TDA, applications of TDA in the service of extracting structure from the (non-summarized) fMRI data itself are heretofore nonexistent. …

Simultaneous Ck2/Tnik/Dyrk1 Inhibition By 108600 Suppresses Triple Negative Breast Cancer Stem Cells And Chemotherapy-Resistant Disease., Katsutoshi Sato, Amol A. Padgaonkar, Stacey J. Baker, Stephen C. Cosenza, Olga Rechkoblit, D.R.C. Venkata Subbaiah, Josep Domingo-Domenech, Alison Bartkowski, Elisa R. Port, Aneel K. Aggarwal, M. V. Ramana Reddy, Hanna Y. Irie, E. Premkumar Reddy

Department of Medical Oncology Faculty Papers

Triple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer stem cell-like cells (BCSCs) have been proposed to represent a chemotherapy-resistant subpopulation responsible for tumor initiation, progression and metastases. Targeting this population could lead to improved TNBC disease control. Here, we describe a novel multi-kinase inhibitor, 108600, that targets the TNBC BCSC population. 108600 treatment suppresses growth, colony and mammosphere forming capacity of BCSCs and induces G2M arrest …