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College of Pharmacy

COBRE Center for Targeted Therapeutics

News Room

2023

A $100,000 COBRE Supplement was awarded to Drs. Rosemary Booze and Michael Shtutman for the study of senicapoc as a novel treatment for HIV related neuropathology.

New cell sorter installed in CTT Microscopy and Flow Cytometry Core.  The Sony SH-800 will extend the range of cell sources which can be sorted in the Core.

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A COBRE Supplement was awarded to Dr. Campbell McInnes for the purchase of peptide synthesizer for the Drug Design and Synthetic Chemistry Core.  

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The CTT Retreat was held from November 30 through December 1, 2023. The retreat included presentations by current project PIs, poster sessions and research talks by distinguished scientists, Dr. Kasper Hansen, University of Montana and Dr. Spyros Artavanis-Tsakonas, Harvard University.

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2022

September 13, 2022: CTT Director Igor Roninson along with co-PIs Eugenia Broude (former CTT investigator) and Hexin Chen were awarded a 5 year National Cancer Institute R01 grant for a project titled “Preventing adaptive drug resistance through Mediator kinase inhibition."

September 13, 2022: The CTT Pilot Project Program awards Rosemarie Booze funding to study if mediator kinase inhibition slows age-related cognitive decline in an animal model.

June 10, 2022: Recently graduated Research Project PI, Sajish Mathew has paper, “Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration” published in Nature Communications.  Read more... 

June 2022: The CTT Pilot Project Program awards Dr. Francisco Leon funding for a project titled, “Exploration in the synthesis of cannabidiol dimers as potential agents to treat neurological disorders."

May 2022:  The NIH/ NIGMS approves the initiation of two new CTT Research Projects: each led by Assistant Professors at the USC School of Medicine.  Dr. Fiona Hollis will lead a project titled, “Targeting neuronal Drp1-Fis1 interactions to mediate glucocorticoid-induced pathologies.” Former Pilot Project leader Joseph McQuail will direct a project titled, “Precision Targeting of Heteromeric NMDA Receptors in Age-Related Memory Disorders.”

May 1, 2022: Former CTT Project PI, Dr. Ozgur Sahin, becomes SmartState Endowed Chair at the Medical University of South Carolina Hollings Cancer Center. Visit the Sahin Lab website for more information. 

April 2022: The Microscopy and Flow Cytometry Core installs two new instruments: an Agilent Cytation 5 with BioSpa for high throughput live cell imaging (funded by the USC ASPIRE program, Dr. Sikirzhytski, PI), and a Seahorse XFe24 metabolic analysis system (funded by an instrumentation supplement to the CTT COBRE, Dr. Roninson, PI and Dr. Norma Frizzell, Co-PI).

March 2022: Research Project leader, Dr. Kathrein (PI) was awarded an R03 grant for $106,274 from NIDDK/NIH for a project titled, “Ing4-deficiency enhances the regenerative capacity of multipotent progenitor cells.”

2021

December 16, 2021: Research Project leader Dr. Ozgur Sahin was awarded a NIH R01 grant, for a project titled “Overcoming chemoresistance in triple negative breast cancer.”

December 2021: Research Project leader Dr. Ozgur Sahin was awarded a grant from the Mary Kay Ash Foundation for the development of novel treatments for HER2 positive breast cancer. Read more... 

September 30, 2021: Functional Genomics Core Director Dr. Michael Shtutman was awarded an NIH R01 grant entitled, “Knowledge discovery and machine learning to Elucidate the Mechanisms of HIV Activity and Interaction with Substance Use Disorder,” for $2,115,541 over 5 years.  

July 2021: Drug Design and Synthesis Core Director Dr. McInnes (PI) was awarded $208,973 from NCI/NIH for a project titled, “Development of non-ATP competitive chemical biology probes to elucidate mechanisms of PLK1 activation and stability.”

July 2021: Internal Advisory Committee Chair and mentor Dr. Kiaris was awarded $487,134 for first year of a 3-year grant of $1M over 3 years from NSF for a project titled, “Sustaining the operation of the Peromyscus Genetic Stock Center."

July 1, 2021: Research Project leader Dr. Ozgur Sahin was awarded a NIH R01 grant for a project titled, “Inhibiting tumor growth and metastasis in highly aggressive breast cancers with centrosome amplification.”

2020

Ozgur SahinMay 15, 2020 - Target project leader Ozgur Sahin publishes paper in Nature Communications, “Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer.” Read more...

Michael Shtutman and Diego AltomareApril 2020 - The CTT Functional Genomics Core, led by Michael Shtutman, in collaboration with College of Pharmacy faculty members Phillip Buckhaults and Michael Wyatt, begins testing health care workers’ samples for COVID-19.

COVID-19March 25, 2020 - The CTT will fund 3-4 Pilot Projects aimed at developing new approaches to COVID-19 treatment or prevention. The grants will vary in amount, depending on justification, and will be available for a full year.

Ozgur SahinJanuary 1, 2020 - CTT Investigator Ozgur Sahin awarded Research Scholar Grant from the American Cancer Society (ACS). Read more…

Joseph McQuailJanuary 2020 - CTT Pilot Grants awarded to Joe McQuail for Precision Targeting of Heteromeric NMDA Receptors in Age-Related Memory Disorders and Taixing Cui for Suppressing stenosis in vein bypass graft surgery.

2019

CTT Symposium AttendeesDecember 5-6, 2019 - Targeted Therapeutics Symposium hosted on the USC campus. The symposium included poster sessions for graduate students and postdocs, presentations from current and past CTT Investigators, and plenary lectures by Katerina Gurova, Roswell Park Cancer Institute, and Jeff Twiss, Chair of the Dept. of Biological Sciences at USC.

Igor RoninsonAugust 1, 2019 -  Center for Targeted Therapeutics awarded another 5 years of the NIH COBRE program with Igor Roninson as Program Director. COBRE Phase II awards are intended to strengthen Phase I centers by further improvements to research infrastructure and the continuation of the development of a critical mass of investigators with shared scientific interests.

CTT NewsFebruary 2019 - Former COBRE research project leader Michy Kelly was awarded a grant through the National Institute on Aging (NIA) for her work on the role of cyclic nucleotide signaling in age-related decline of social memories. 

Advancements in Colon Cancer Treatment Pioneered by College of Pharmacy Faculty Member & Researcher Dr. Igor Roninson & His Research Team, Which Includes University Students, in ColumbiaJanuary 2019 - A promising new class of drugs for the treatment of colon cancer is emerging, due to research and work done at the University of South Carolina College of Pharmacy under the guidance of Igor Roninson.

2018

Gary LandrethNovember 2018 - The Center for Targeted Therapeutics hosted its' two day symposium highlighting the work down through COBRE. The featured guest speaker was Gary Landreth from the University of Indiana who spoke about his work with Alzheimer's. Also featured were presentations from faculty members updating their research findings. Graduate students and faculty shared posters highlighting their work and Kendall Murphy from R. Michael Gower's lab won the poster award. 

InhibinOctober 2018 - Former COBRE Project Leader Mythere Karthikeyan was awarded a grant through the National Cancer Institute for her work on inhibin function in tumor angiogenesis. 

Tumor researchSeptember 2018 - The American Cancer Society awarded a research pilot grant for the SOAR (Supporting Outstanding Academic Research) to Mythreye Karthikeyan and Eugenia Broude titled "Therapeutic Impact of Epigenetically Regulated GDF2/BMP9 in Ovarian Cancer."  Grant reviewers hope that this grant will serve as the foundation for a R01 or similar competitive grant. 

CTT Rekha PatelMay 1, 2018 - Former Pilot Project PI, Rekha Patel's grant “Dysregulation of the PACT-mediated crosstalk between protein kinases PKR and PERK contributes to dystonia 16 (DYT16)”

2017

Jing Fang - leukemiaAugust 1, 2017 - Targeting the p62 signalosome in leukemia” - Jing Fang’s new groundbreaking research addresses issues with patients with certain subtypes of leukemia associated with dismal outcomes due to resistance to current treatment options, particularly for those with MLL rearrangements. Chronic NF-kB activity is observed in leukemia cells, especially within the leukemia stem cell (LSC) population, and is implicated as a requirement for leukemogenesis, including the MLL-driven leukemia. Given the pleotropic function of NF-kB, targeting the leukemia-specific function of NF-kB is urgently needed.  The proposed study will help identify and understand the function and mechanism of leukemia-specific p62 signaling pathways in the development of leukemia.  This, in turn, will shape design novel targeted therapy that aims to suppress leukemia cells, but preserve normal cells. 

Michy Kelly X-ClarityJuly 1, 2017 - Michy Kelly will work with other faculty at the USC School of Medicine to acquire Logos X-ClarityTM Tissue Clearing System and Confocal Microscopy Objective for the USC Instrumentation Resource Facility.

CTT News Aspire-II fundingJuly 1, 2017 - Rekha Patel is teaming up with other USC researchers to study chronic social stress and accelerated aging among South Carolina women.  The team is comprised of faculty from Biological Sciences, Epidemiology and Biostatistics, Nursing, and the Arnold School of Public Health.  Specifically, they will investigate the social, behavioral, and biological influences on aging processes.

Eugenia Breast Cancer researchJuly 1, 2017 - Eugenia Broude, Target PI, received a NIH/NCI grant “CDK8/19 inhibitor for the treatment of HER2+ breast cancer.”  The aims of this study will investigate whether Senexin B potentiates the effect of the trastuzumab/pertuzumab (T+P) combination, the current first line standard-of-care for HER2+ breast cancers, in vitro and in vivo, and whether Senexin B prevents the development of resistance to T+P.  Broude’s research will test if cells selected for acquired T+P resistance and T+P treated tumors overexpress CDK8, as a possible patient selection criterion for the initial clinical development. She will also determine if treatment with T+P combined with Senexin B, in vitro and in vivo, decreases the phosphorylation of HER2- and CDK8-regulated transcription factors, as potential markers of treatment response.  With approximately 20% of breast cancers characterized as HER2-positive, and patients with such cancers treated with HER2-targeting drugs (such as Herceptin), nearly 70% of patients with metastatic HER2-positive breast cancer do not respond to HER2-targeting therapy and almost all of the initially responsive cancers eventually become resistant. Broude's team have found that a non-toxic drug acting on proteins called CDK8/19 overcomes resistance to HER2-targeting drugs and prevents such resistance from developing.  This research proposes a program of studies that will lead to combining this drug with HER2-targeting therapies in the treatment of patients with metastatic HER2-positive breast cancer.

Xu Michy Alzheimer'sMarch 1, 2017 -  With this award, “Brain targeted nanoparticle for Alzheimer's disease therapy,” Peisheng Xu and Michy Kelly will develop a NAC-DTDRN and characterize its BBB penetration efficiency in vitro and evaluate the anti-inflammatory and anti-oxidant effects of the NAC-DTDRN in vitro and study its pharmacokinetics in vivo.  This study will test the efficiency of the NAC-DTDRN in an AD animal model and evaluate its toxicity.  This research will develop a nanoparticle based brain targeted delivery system for the immunotherapy of Alzheimer’s disease by taking advantage the unique characteristics of the brain tissue.

Ortinski NeuronFebruary 1, 2017 - COBRE Pilot Project PI, Pavel Ortinski, seeks to address the obstacle to developing effective drug addiction therapies – drug-induced plasticity is often restricted to discrete neuronal populations within brain reward areas. The goal of this research is to investigate mechanisms that assemble medium spiny neuron (MSN) microcircuits underlying behavioral expression of cocaine seeking and taking. We propose that release of neuroactive molecules from astrocytes, a type of non-neuronal brain cell, facilitates changes within neurons specifically associated with cocaine experience. Identification and isolation of neuronal populations that drive cocaine-directed behavior may facilitate development of targeted addiction therapeutics while expanding fundamental understanding of astrocyte-neuron interactions.

NeurotoxicityFebruary 1, 2017 - In his new research, “Functional identification of new mechanisms of neurotoxicity induced by HIV and drugs of abuse,” Michael Shtutman seeks to set a standard model approach for understanding how HIV and drugs of abuse promote neuronal damage and death, including both direct and indirect effects of HIV proteins in combinations with opiates and stimulants. Furthermore, these approaches can then be applied to a variety of systems from primary neuronal culture to animal models of HAND, to further explore novel therapeutic targets for treatment of HAND.  HIV Associated Neurocognitive Disorder (HAND) is among the most common and clinically important complications of HIV infection.  The project will determine new mechanisms of synergistic neurotoxicity of HIV Tat and cocaine, with the results leading to the discovery of new targets for the development of HAND therapy.

 2016

Mitochondrial nd5July 1, 2016 - Rekha Patel is teaming up with other USC researchers to study the influence of mitochondrial ND5 sequence on average lifespan of Daphnia pulex.  The team includes faculty from Biological Sciences and the Department of Pharmacology, Physiology, and Neuroscience from the USC School of Medicine. 

Grillo Feeding BehaviorMay 15, 2016 - COBRE Pilot Project PI, Claudia Grillo, received a NSF grant “Identifying a new circuit that controls feeding behavior: leptin and serotonin interactions.”  Feeding is an essential activity for the maintenance of life, and its regulation is associated with multiple brain mechanisms that work together to ensure that animals eat appropriately. The complexity of these interactions has presented challenges to our efforts to fully appreciate the neural basis of food intake. However, before we can understand that complexity we must first identify the individual brain circuits that regulate food intake. The main goal of this project is therefore to use advanced genetic and anatomical approaches to identify a novel circuit that contributes to the control of feeding behavior. Identifying this circuit will ultimately allow us to determine how it works together with other feeding circuits that we already know more about to regulate a complex behavior critical for animal survival. In achieving that goal the work will not only increase our understanding of fundamental principles associated with how the brain regulates behavior, but may also lead to unexpected insights into feeding disorders and the chronic medical conditions associated with them that create considerable economic and social burdens, nationally and globally. In addition, this project includes a Summer Internship Program that will provide an integrated research experience for undergraduate students, particularly students who will be recruited from populations that are under-represented in science and medicine. These research experiences will provide such students with experiential learning opportunities that will create a foundation for future success in biomedical or basic research science.

2015

Mitochondrial StressSeptember 1, 2015 - Norma Frizzell's grant hypothesizes that mitochondrial stress results in the accumulation of fumarate and that succination alters protein structure or function contributing to disease pathology.  It identifies several succinated targets already and mechanistically addresses how succination of these leads to further reductions in mitochondrial function.  The study will use a molecular strategy to distinguish the bioenergetic defect from protein succination and investigate therapeutic strategies designed to reduce fumarate and succination leading to improvements in mitochondrial function and the disease phenotype.  This work will directly assess how a protein modification derived from a mitochondrial metabolite contributes to the development of neuropathology during Leigh Syndrome. By demonstrating the significance of this pathway in the progression of disease pathology, we will be able to design novel targeted therapeutic strategies for the effective treatment of mitochondrial diseases.

TRp disfunctionAugust 7, 2015 - Georgi Petkov’s grant, “Role of TRP channels in human detrusor function and disfunction” will use multiple state-of-the-art approaches including single-cell RT-PCR, qPCR, Western blot, in situ proximity ligation assay, confocal immunohistochemical and immunocytochemical analyses of DSM whole tissue and single cells to identify the TRPM4 channel expression and localization in human DSM cells from control and OAB patients.  The research will reveal unknown mechanisms of human urinary bladder function and regulation in health and disease. 

Frizzell - diabetesAugust 1, 2015 - The expansion of adipose tissue is associated with the development of insulin resistance and Type 2 diabetes. Given that approximately 26 million Americans have diabetes and an estimated 79 million have prediabetes, the role of expanding adipose tissue mass in the development of systemic metabolic dysfunction has received increased attention. However, many of the biochemical mechanisms underlying adipocyte metabolic dysfunction remain unclear. Norma Frizzell's research explores the early metabolic changes in the adipocyte and anticipates that these studies will lead to better targeted therapies for the early treatment of diabetes.

ovaries cancer XuJuly 1, 2015 - Peisheng Xu's award, “Nano-cocktail Overcomes Multidrug-Resistance for Ovarian Cancer Therapy” explores drug combinations for optimal cancer cell proliferation inhibitory effect and examines the dual-ligand targeting effect on the biodistribution of DTNC and investigate its pharmacokinetic properties.  The study evaluates the tumor growth inhibitory effect of DTNC in both subcutaneous xenograft and orthotopic intraperitoneal tumor mouse models and examine its systemic toxicity. This research will develop a nano-cocktail for the treatment of ovarian cancer through a dual-targeting strategy to carrier a drug combination which can kill cancer stem cells and drug resistant cells as well as stop the metastasis of cancer.

atrophy TRb3June 1, 2015 - Ho-Jin Koh, former pilot project PI, will determine TRB3 expression and function in response to skeletal muscle denervation and anticipates that overexpression of TRB3 in muscle will worsen muscle atrophy. The proposed research will establish the novel function of TRB3 on muscle atrophy and identify a new approach for treating muscle atrophy. In addition, the study will provide evidence to investigate the role of TRB3 in other muscle diseases related to muscle atrophy, including muscle disuse, cachexia, and sarcopenia. The loss of muscle mass (atrophy) is one of the medical consequences of many diseases, including cancer, neurodegenerative diseases and autoimmune diseases, and results in serious health problems. The exact causes of muscle atrophy are not known, and this study will investigate the role that a protein, TRB3, may play in mediating one type of muscle loss.

long term memory - michy kelly2015 - 2017 - The Brain and Behavior Research Foundation awarded Michy Kelly's grant “Dissecting the molecular and anatomical pathways of recent versus remote long-term memory.”

2014

vhipp kellyJuly 8, 2014 - Michy Kelly’s study will determine where (VHIPP vs. dorsal HIPP) and when (adulthood vs. adolescence) PDE11A modulates social behaviors and identify how social isolation modifies PDE11A compartmentalization and, thus, impairs subsequent social behaviors.  In addition, the research will define the signals that control the subcellular localization of PDE11A.  Finally, the proposal seeks to better understand how compartmentalization of cyclic nucleotide signaling in the ventral hippocampal formation regulates social behaviors with the goal of identifying new therapeutic targets for social deficits.

 

 


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