Medicine and Health Sciences Commons^™

Aromatase Inhibitors Plus Weight Loss Improves The Hormonal Profile Of Obese Hypogonadal Men Without Causing Major Side Effects, Georgia Colleluori, Rui Chen, Christie G Turin, Francesca Vigevano, Clifford Qualls, Biju Johnson, Sanjay Mediwala, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).

Design: Randomized double-blind placebo-controlled pilot trial.

Methods: …

Hypomorphic Si Genetic Variants Are Associated With Childhood Chronic Loose Stools., Bruno P Chumpitazi, Jeffery Lewis, Derick Cooper, Mauro D'Amato, Joel Lim, Sandeep Gupta, Adrian Miranda, Natalie Terry, Devendra Mehta, Ann Scheimann, Molly O'Gorman, Neelesh Tipnis, Yinka Davies, Joel Friedlander, Heather Smith, Jaya Punati, Julie Khlevner, Mala Setty, Carlo Di Lorenzo

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The SI gene encodes the sucrase-isomaltase enzyme, a disaccharidase expressed in the intestinal brush border. Hypomorphic SI variants cause recessive congenital sucrase-isomaltase deficiency (CSID) and related gastrointestinal (GI) symptoms. Among children presenting with chronic, idiopathic loose stools, we assessed the prevalence of CSID-associated SI variants relative to the general population and the relative GI symptom burden associated with SI genotype within the study population.

METHODS: A prospective study conducted at 18 centers enrolled 308 non-Hispanic white children ≤18 years old who were experiencing chronic, idiopathic, loose stools at least once per week for >4 weeks. Data on demographics, GI …

Rna Sequencing Of Human Peripheral Nerve In Response To Injury: Distinctive Analysis Of The Nerve Repair Pathways., Andrew S. Welleford, Jorge E. Quintero, Nader El Seblani, Eric Blalock, Sumedha Gunewardena, Steven M. Shapiro, Sean M. Riordan, Peter Huettl, Zain Guduru, John A. Stanford, Craig G. Van Horne, Greg A. Gerhardt

Manuscripts, Articles, Book Chapters and Other Papers

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson's disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another …

Acute Lymphoblastic Leukemia Presenting Initially As Spinal Cord Compression: When Chemotherapy Alone Is Enough, Albert Jang, Kallie N Kram, Scott N Berger, Mahmoud R Gaballa, Lee B Lu, David R Dunaway, Courtney N Miller-Chism

Faculty, Staff and Students Publications

Spinal cord compression (SCC) is a rare initial presentation and complication of acute lymphoblastic leukemia (ALL) with nearly all reported cases occurring in the pediatric population. We report a 38-year-old previously healthy man who presented with acute on chronic lower back pain, gait instability, urinary retention, and severe thrombocytopenia. Radiologic examination revealed two soft tissue masses of the thoracic spine associated with compression fractures causing spinal canal narrowing and cord compression. Bone marrow biopsy confirmed the diagnosis of ALL. Immediate initiation of high-dose corticosteroids and systemic chemotherapy resolved the patient's symptoms without radiation therapy or surgical intervention. After two courses …

Spironolactone In Pulmonary Arterial Hypertension: Results Of A Cross-Over Study, Zeenat Safdar, Adaani Frost, Arya Basant, Anita Deswal, E O'Brian Smith, Mark Entman

Faculty, Staff and Students Publications

The renin–angiotensin–aldosterone system is implicated in the pathophysiology of pulmonary arterial hypertension. We undertook this study to determine the effects of spironolactone, a mineralocorticoid receptor blocker, on collagen metabolism in pulmonary arterial hypertension patients. After obtaining institutional review board approval and informed consent, 42 pulmonary arterial hypertension patients were prospectively enrolled and 35 patients completed the 16-week randomized double-blinded crossover clinical trial. Subjects received 50 mg spironolactone or placebo and at the end of week 8, treatment arm was switched. Circulating levels of collagen biomarkers, brain natriuretic peptide, and aldosterone levels were measured, and six-minute walk distance, liver function tests, …

Metaproteomic Analysis Of Human Gut Microbiome In Digestive And Metabolic Diseases, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Metaproteomics, as a subfield of proteomics, has quickly emerged as a pivotal tool for global characterization of a microbiome system at a functional level. It has been increasingly applied in studying human digestive and metabolic diseases, and provides information-rich data to identify the dysbiosis of human gut microbiome related to healthy or disease states to elucidate the molecular events underlying host-microbiota interplays. While significant technical challenges still exist, this emerging technology has been demonstrated to provide essential information in interrogating functional changes in the human gut microbiome, complementary to metagenomics and metatranscriptomics. This chapter overviews the overall metaproteomic work flow …

Extracellular Mitochondria Released From Traumatized Brains Induced Platelet Procoagulant Activity, Zilong Zhao, Yuan Zhou, Tristan Hilton, Fanjian Li, Cha Han, Li Liu, Hengjie Yuan, Ying Li, Xin Xu, Xiaoping Wu, Fangyi Zhang, Perumal Thiagarajan, Andrew Cap, Fu-Dong Shi, Jianning Zhang, Jing-Fei Dong

Faculty, Staff and Students Publications

Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant. In testing this hypothesis experimentally, we found that the extracellular mitochondria purified from brain trauma mice and those released from brains subjected to freeze-thaw injury remained metabolically active and produced reactive …

Lisinopril-Induced Angioedema In A Patient With Plasma Prekallikrein Deficiency, Swapan K Dasgupta, Stefanie Rivera, Perumal Thiagarajan

Faculty, Staff and Students Publications

Angiotensin-converting enzyme (ACE) inhibitors are extensively prescribed to treat patients with hypertension, congestive heart failure, and diabetic nephropathy. A small fraction of these patients (approximately 0.7%) develop angioedema, manifested by swelling of the lips and oropharynx. Angioedema of oropharynx is a medical emergency that can lead to asphyxiation and death. The angioedema is due to bradykinin generated from high molecular weight kininogen by kallikrein, which is derived from plasma prekallikrein by action of the factor XIIa, factor Xia, or prolylcarboxypeptidase. Bradykinin induces vasodilation and increased vascular permeability. ACE is the major degrading enzyme of bradykinin in the intravascular department. ACE …

Hypogonadism, Type-2 Diabetes Mellitus, And Bone Health: A Narrative Review, Vittoria Russo, Rui Chen, Reina Armamento-Villareal

Faculty, Staff and Students Publications

One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could …

Sirt3 Promotes Lipophagy And Chaperon-Mediated Autophagy To Protect Hepatocytes Against Lipotoxicity, Tian Zhang, Jingxin Liu, Shengnan Shen, Qiang Tong, Xiaojun Ma, Ligen Lin

Faculty, Staff and Students Publications

Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs) breakdown, to initiate lipolysis via either cytosolic lipases or macroautophagy. SIRT3, a mitochondrial NAD+-dependent deacetylase, regulates the acetylation status and activity of many substrates involving in energy metabolism. However, the role of SIRT3 in regulating lipophagy is controversial. The current study showed that SIRT3 expression was decreased and the macroautophagy flux was blocked in the primary hepatocytes from high-fat diet fed mice and P/O (palmitic acid and oleic acid mixture) treated AML12 mouse hepatocytes, compared with the corresponding controls. …

Classification Models Of Idiopathic Pulmonary Fibrosis Patients, Mohammed Alqawba, Luis R. Rodriguez, Norou Diawara, Rebecca T. Beuschel, Maryann Kaler, Amisha V. Barochia, Stewart J. Levine, Steven D. Nathan, Geraldine Grant

Mathematics & Statistics Faculty Publications

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal interstitial lung disease with no current cure. Progression of IPF is difficult to predict as the clinical course can be highly variable and range from a rapidly deteriorating state to a relatively stable state, or may be characterized by a slow progressive decline. Therefore, the need for an accurate diagnosis and improved tools for monitoring and managing IPF is of paramount importance, all for understanding the mitochondrial structure and the function played in the IPF. Mitochondrial DNA copy number (MtDCN) has been correlated with mortality in IPF patients and is a …

A Case Of Ana-Negative Systemic Sclerosis Treated With Methylprednisolone, Carminda P. Rogacion, Veronica S, Uy, Reynaldo L. Ugalde, Emmerson Gale S. Vista

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Systemic sclerosis is a multi-systemic disease characterized by excessive fibrosis, inflammation, and vasculopathy. Common clinical features include skin thickening, telangiectasias, salt and pepper skin, beak-shaped nose, and microstomy. We report a case of ANA-negative systemic sclerosis in a male patient.

Case illustration: Our patient presented with a 10-month history of diffuse hyperpigmentation, skin tightening and decreased mouth aperture, accompanied by digital ulcers, hypopigmented macules and violaceous discoloration of the digits upon exposure to cold temperature. Punch biopsy done revealed mild acanthosis of the epidermis with basal cell layer hyperpigmentation, vacuolar alteration and thickening of the basement membrane …

Predictive Modeling Of Influenza In New England Using A Recurrent Deep Neural Network, Alfred Amendolara

Theses

Predicting seasonal variation in influenza epidemics is an ongoing challenge. To better predict seasonal influenza and provide early warning of pandemics, a novel approach to Influenza-Like-Illness (ILI) prediction was developed. This approach combined a deep neural network with ILI, climate, and population data. A predictive model was created using a deep neural network based on TensorFlow 2.0 Beta. The model used Long-Short Term Memory (LSTM) nodes. Data was collected from the Center for Disease Control, the National Center for Environmental Information (NCEI) and the United States Census Bureau. These parameters were temperature, precipitation, wind speed, population size, vaccination rate and …

Association Between Obesity And History Of Atopy With Atopic Dermatitis In Children: A Cross-Sectional Study, Putu Nila Wardhani Batan, Ariana Ariana, Made Wardhana

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: The prevalence of atopic dermatitis (AD) has rapidly increased in the past 4 decades and has been mostly observed in children. The prevalence of obesity has also significantly increased worldwide, suggesting that the two conditions may be associated.

Methods: This retrospective analytic study involved a cross-sectional design and used secondary data taken from the medical record of patients who visited the Pediatric Dermatology Subdivision at Dermatology and Venereology Polyclinic Sanglah General Hospital from January 2015 to December 2015. Thirty-two samples were selected.

Results: The prevalence ratio of obesity among subjects with AD was 2.178 (95% CI …

Treatment Of Multibacillary Leprosy Following The Development Of Dapsone Hypersensitivity Syndrome, Sudarsono Sudarsono

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: World Health Organization (WHO) multi-drug therapy (MDT) is the current standard treatment for leprosy. A wide range of frequency of adverse effects caused by MDT has been reported. Dapsone hypersensitivity syndrome (DHS) is a serious adverse effect caused by dapsone. Prompt withdrawal of dapsone is important aspect in the management of DHS. Alternative regimens are needed to treat leprosy patient with DHS.

Case Illustration: A 37-year-old man with multibacillary (MB) leprosy developed DHS in 39 days after the initiation of WHO MDT. Dapsone was withdrawn and methylprednisolone of 75 mg/day was prescribed. Twelve days after admission the …

Prevalence And Risk Factors Of Bacterial Vaginosis Among Female Sex Workers In Surakarta, Rini Hastuti, Danu Yuliarto, Agung Triana, Willa Damayanti, Rakhma Tri Irfanti, Mardiana Mardiana, Putti Fatiharani Dewi, Ambar Aliwardani, Ervianti Abas, Sulistyo Sulistyo, Prasetyadi Mawardi, Endra Yustin Ellistasari

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Bacterial vaginosis (BV) is the most common vaginal infection in women of reproductive age and increases the risk of acquiring human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs). Data regarding the association between sexual activity and BV acquisition is contradictory. Thus, tracking the prevalence and associated risk factors of BV among female sex workers (FSWs) is necessary to improve our understanding and control of STDs and the HIV epidemic.

Methods: The subjects of this study were FSWs in Surakarta. This study adopted a cross-sectional design, and diagnosis was established using Amsel criteria. Interviews were conducted …

The Epidemiology Of Skin Cancer At Dr. Cipto Mangunkusumo National Central General Hospital From 2014 To 2017, Larisa Paramitha Wibawa, Melody Febriana Andardewi, Inge Adi Kristanti, Riesye Arisanty

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: The incidence of skin cancer has been increasing over the past decades globally. At present, there is no valid national cancer data in Indonesia. The purpose of this study is to evaluate the increment of skin cancer cases at Dr. Cipto Mangunkusumo National General Hospital, Jakarta.

Methods: In this retrospective descriptive study, we evaluated all pigmented skin tumor cases from June 2014 to June 2017. Data were obtained from the Department of Anatomical Pathology and medical records at Dr. Cipto Mangunkusumo National General Hospital. Data were compared with previous reports.

Results: From 263 skin cancer cases, …

Langerhans Cell Histiocytosis: Diagnosis And Management, Lusiana Lusiana, Hikari Ambara Sjakti, Githa Rahmayunita, Tjut Nurul Alam Jacoeb, Inge Ade Krisanti

Journal of General - Procedural Dermatology and Venereology Indonesia

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by abnormal clonal proliferation of Langerhans dendritic cells. The incidence of LCH is 1 to 3 cases per 1 million children worldwide, and occurs most frequently in children of 1–4 years of age. The etiopathogenesis of LCH, whether it is neoplastic or reactive, is still controversial. Langerhans cell histiocytosis has a wide spectrum of clinical features, and dermatological abnormalities usually occur early. The most frequent lesions are elevated yellowish-red translucent papules about 1–2 mm in diameter and generally located in seborrheic areas. The most recent classification (the Histiocyte Society study 2017) …

The Use Of Systemic Medications In Pediatric Dermatoses: A Review, Shanthi Narla, Githa Rahmayunita, Rinadewi Astriningrum, Tor Shwayder, Ariyati Yosi, Henry W. Lim

Journal of General - Procedural Dermatology and Venereology Indonesia

Research has begun to illustrate a favorable efficacy and side-effect profile for many systemic agents used in pediatric dermatological conditions (i.e. atopic dermatitis, psoriasis, scleroderma, alopecia areata, chronic spontaneous urticaria, autoimmune blistering disorders, and hidradenitis suppurativa) despite not having extensive randomized clinical trials. The purpose of this article is to summarize the available data on the treatment regiments, safety, and efficacy of systemic immunosuppressants, including the newer biologics, focusing on the most up-to-date systematic reviews or randomized clinical trials. The review demonstrates that many of the present studies lack data on long-term efficacy and consist of small patient populations. Further …

Recurrent Basal Cell Carcinoma With Maxillary Bone Invasion, Adhimukti T. Sampurna, Eva Riani, Inge Ade Kristanti, Yayi Dwina, Kuniaki Ohara

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Basal cell carcinoma (BCC) is a malignant, slow growing, and locally invasive skin tumor. Advanced and neglected BCC may invade adjacent structures. The 5-year recurrence rates of facial BCCs are 4.1% after excision and 2.5% after Mohs Micrographic Surgery (MMS). The number of BCC cases invading the bones of the head and neck region is limited.

Case Illustration: A 75-year-old male complained of bleeding and ulcer enlargement on the right cheek expanding to the right nasal ala for 1 month. The patient had a history of an enlarged and painful lenticular nodule with a hyperpigmented spot that …

Mers-Cov Infection In South Korea And Strategies For Possible Future Outbreak: Narrative Review, Chulwoo Park

Faculty Publications

Although there were some positive viewpoints from international press and academia that the Republic of Korea (hereafter South Korea) successfully controlled the Middle East Respiratory Syndrome (MERS) outbreak in 2015, the domestic point of view towards the MERS response in South Korea was critical. As people in the world’s 11th largest economy, South Koreans criticized the failure of hospitals’ initial response to the MERS index case and the lack of a proper control strategy for secondary and tertiary cases. To contain the MERS outbreak, South Korea implemented mainly three MERS control and intervention strategies: quarantine and isolation system, temporary closure …

Oral Manifestations Of Renal Osteodystrophy In A Patient With Systemic Lupus Erythematosus With Chronic Renal Failure And Secondary Hyperparathyroidism: A Case Report, Inthivorn Riyachan, Ajiravudh Subarnbhesaj, Wilairat Sarideechaigul, Poramaporn Klanrit

Journal of Dentistry Indonesia

Systemic lupus erythematosus (SLE) is one of the chronic autoimmune diseases that leads to multiple manifestations in several organ systems, including chronic renal failure (CRF). Renal osteodystrophy (ROD) is one of the most common complications of CRF associated with secondary hyperparathyroidism (HPT). A combination of CRF and HPT can result in broad-spectrum disorders in the metabolism of minerals such as calcium, phosphorus, and vitamin D, which can affect bone turnover, mineralization, and volume. Radiographic alterations of ROD are considered as one of the earliest signs of CRF. Objective: To describe the oral manifestations in both the maxilla and mandible of …

Chemical Composition And Behavioural Responses Of Male And Female Bactrocera Dorsalis To Their Volatile Emissions, Fikira Kimbokota

Journal of Humanities and Social Sciences

Bactrocera dorsalis, (Tephritidae) presented a grave threat to a broad range of fruit and vegetables in the tropics, including Tanzania. Bactrocera dorsalis is among the most destructive tephritid fruit fly, causing devastating loss of fruits especially mango. Insects use olfactory cues to locate hosts, oviposition sites and mating, in which pheromones are believed to be a strong cue used by insect to locate their mates. However, due to their high ability to adapt and occupy different ecological niches into various agroecological zones, there is a need to evaluate pheromonal composition from time to time to improve their control strategies. Therefore, …

Cholangiocarcinoma Presenting As Humoral Hypercalcemia Of Malignancy: A Case Report And Literature Review, Burak Erdinc, Preethi Ramachandran, Ruchi Yadav, Sonu Sahni, Gardith Joseph

Touro College of Osteopathic Medicine (New York) Publications and Research

Humoral hypercalcemia of malignancy (HHM) is most commonly encountered in squamous cell carcinoma (SCC) of different organs, and It is characterized by elevated parathyroid hormone-related peptide (PTHrP) levels. It may be seen as a manifestation of cholangiocarcinoma (CCC) at presentation and later in the course of the disease. However, HHM due to intrahepatic cholangiocarcinoma is a rare association and is associated with a poor prognosis. We herein report a case of hypercalcemia presenting as the first manifestation of an underlying rare variant of intrahepatic cholangiocarcinoma. Our patient is a 57-year-old male who presented to the emergency room with severe symptoms …

Cognitively Normal Women With Alzheimer’S Disease Proteinopathy Show Relative Preservation Of Memory But Not Of Hippocampal Volume, Jessica Z.K. Caldwell, Jeffrey L. Cummings, Sarah J. Banks, Sebastian Palmqvist, Oskar Hansson

School of Medicine Faculty Research

Background: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Methods: We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. Results: Amyloid-positive (Aβ/P-tau+) CN women …

Rates Of Benign Heart Tumors Diagnosed In Florida Hospitals: 1988-2012, Robert B. Hood, Elliott Smith, Richard B. Early, Zachary Weber, Sharona B. Ross, Alexander S. Rosemurgy Ii, Randall E. Harris

Florida Public Health Review

No abstract provided.

Design And Biological Evaluation Of Colchicine-Cd44-Targeted Peptide Conjugate In An In Vitro Model Of Crystal Induced Inflammation, Khalid A. Zoghebi, Emira Bousoik, Keykavous Parang, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is an inflammatory arthritis due to the joint deposition of monosodium urate (MSU) crystals. Phagocytosis of MSU crystals by tissue macrophages results in the generation of reactive oxygen species (ROS) and production of inflammatory cytokines and chemokines. Colchicine use in gout is limited by severe toxicity. CD44 is a transmembrane glycoprotein that is highly expressed in tissue macrophages and may be involved in gout pathogenesis. The P6 peptide is a 20-amino acid residue peptide that binds to CD44. We hypothesized that the conjugation of colchicine to the P6 peptide would reduce its off-target cytotoxicity while preserving its anti-inflammatory effect. …

Delivery Of Small Molecule And Rna Using Synthetic Polymeric Micelles And Multifunctional Exosomes For The Treatment Of Type 1 Diabetes, Yang Peng

Theses & Dissertations

Type 1 diabetes is one of the most challenging chronic autoimmune diseases. The destruction and dysfunction of insulin-secreting β cells are the results of inflammatory infiltration and the synergistic effect of multiple immune cells. The aim of this dissertation is to develop novel and reliable therapeutic approaches to advance the treatment of T1D: including chemical modification of a broad-spectrum immunosuppressant, co-application of small molecule based immune intervention and siRNA based β cell preservative therapy, and administration of a PI3K-δ/γ dual inhibitor to specifically target immune cells, utilizing synthetic polymeric micelles or natural produced multi-functional exosomes derived from human bone marrow …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

The Role Of Histone Chaperone Fact Complex In Base Excision Repair Pathway And Its Therapeutic Potential In Colon Cancer And Medulloblastoma, Heyu Song

Theses & Dissertations

Base excision repair (BER) pathway is required for the removal of damaged bases caused by alkylation, oxidation and ring-saturation. Human apurinic/apyrimidinic endonuclease 1 (APE1) plays a central role in BER pathway. Although repair of damaged bases by recombinant APE1 has been well investigated in vitro, how APE1 gains access to damaged bases in the context of chromatin is largely unknown. A prominent member of the histone chaperone family, FACT (Facilitates Chromatin Transcription) is thought to reorganize nucleosomes through the destabilization of multiple intra-nucleosome contacts. FACT complex is composed of two polypeptides identified as SPT16 (Suppressor of Ty 16) and SSRP1 …