Medical Specialties Commons^™

Absence Of Motor Impairments Or Pathological Changes In Tmem230 Knockout Rats, Wenjuan Zhang, Hao Peng, Daihe Yang, Guohua Song, Juan He, Yun Zhou, Cao Huang, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson's disease (PD), which is the second most common neurodegenerative disorder, is characterized by progressive movement impairment and loss of midbrain dopaminergic neurons in the substantia nigra. Although mutations in TMEM230 are linked to familial PD, the pathogenic mechanism underlying TMEM230-associated PD remains to be elucidated. To explore the effect of TMEM230 depletion in vivo, we created TMEM230 knockout rats using CRISPR-Cas9 technology. TMEM230 knockout rats did not exhibit any core features of PD, including impaired motor function, loss of dopaminergic neurons in the substantia nigra, or altered expression of proteins related to autophagy, the Rab family, or vesicular trafficking. …

Exploring The Benefits Of Blazepod Technology Through An Occupational Therapy Lens, Carson Bryan, Cynthia Haynes

Summer 2024 OTD Capstone Symposium

BlazePod technology is an intervention used successfully in Physical Therapy (PT) to address motor coordination deficits, however, there is limited evidence that OTs can successfully use it as a preparatory intervention with individuals who have motor coordination and cognitive deficits and are unable to independently complete everyday occupations such as dressing, bathing, toileting, etc.

The focus of this project was to provide evidence that supports how the occupational therapy profession can utilize BlazePod technology as a preparatory intervention tool to address motor coordination and cognitive deficits that in turn will enhance ADLs and IADLs.

Cycle Syncing: Optimizing Women's Quality Of Life, Megan Francois

Theses and Graduate Projects

A woman’s hormones are in constant fluctuation throughout the menstrual cycle. This 28-day, on average, fluctuation can cause major shifts in mood, cognition, exercise tolerance, and nutrition needs. Because of this, there is potential to optimize quality of life if each phase is synced with diet, exercise, and complementary medicine utilizing holistic methods. Implications for further research include a need for additional longitudinal and prospective studies. Factors that need to be addressed include further analysis of the windows of vulnerability over the menstrual cycle according to female hormone fluctuations, effects of hormonal contraceptives, and effects of pathology on the cycle.

Preserving Pediatric Wellness: Enhanced Recovery After Surgery Protocols And Pain Management In Pediatric Surgery, Kimberly Kim

Theses and Graduate Projects

Background: Enhanced recovery after Surgery (ERAS) protocols and multimodal pain management strategies have revolutionized perioperative care in adult surgical practice by leading to improved postoperative outcomes and better pain management. However, the adoption of these protocols to pediatric surgical care remains underexplored.

Purpose: This systematic review aims to examine recent randomized clinical trials on the implementation of ERAS protocols and multimodal pain management strategies in pediatric surgical patients.

Methods: A computer-based literature search of databases through Google Scholar and PubMed with manual reference searches was used to identify eligible studies. The review includes randomized controlled trials focusing on multimodal pain …

Queering Pa School: An Audit Of Augsburg University’S Physician Assistant Program Regarding Lgbtq+ Related Health Topics, Annika Kuchar

Theses and Graduate Projects

Background: Historically LGBTQ+ people have encountered discrimination in the world of medicine, and often providers are sometimes unaware of how to manage medical issues of these patients. In order to best serve queer and trans patients, a more coherent, consistent curriculum needs to be established so that all medical professions are capable of giving high quality treatment to these patients. Physician assistants (PAs) are advanced practice providers who take care of LGBTQ+ patients on a daily basis and are trained under a similar model as physicians. PA programs must also be up to date on the most culturally sensitive ways …

Barriers Primary Care Physician Assistants Face In Referring Patients To Palliative Care Services Early In The Disease Process, Claire Petersen

Theses and Graduate Projects

Background: Medical specialties such as hospice and palliative care have been proven to improve quality of life for patients facing end-of-life and chronic illness. Though increasing awareness of these specialties has resulted in greater availability, it is essential to investigate the barriers clinicians, such as Physician Assistants, face in making these referrals in order to provide quality healthcare to those who need it. Physician Assistants specifically are an essential clinician group to evaluate, as they continue to become more prevalent in the healthcare system.

Purpose: To determine barriers primary care Physician Assistants face when identifying candidates for and referring to …

Long-Term Neurodevelopmental Outcomes Post-Chronic Midazolam Exposure During Early Life, Nghi M. Nguyen

Theses & Dissertations

In recent decades, the rising number of neonates born in the Neonatal Intensive Care Unit (NICU) due to prematurity has raised concerns about their overall well-being and development. Premature neonates are at higher risk of health complications and often require invasive procedures. These invasive procedures often induce stress and agitation, prompting physicians and healthcare providers to provide sedation or general anesthesia to manage discomfort. Epidemiological studies of human patients have revealed a correlation between childhood exposure to general anesthetic and sedative agents and subsequent cognitive deficits. This association is also supported in animal models, which shows that exposure to anesthetics …

Development Of A Sensory-Based Intervention Manual For Educators, Bralie Dent, Zeida Gutierrez

Summer 2024 OTD Capstone Symposium

This project focused on the development of an educational manual on sensory processing disorder (SPD) for educators. The manual was created as a resource to enhance teachers' understanding of SPD and confidence in implementing sensory-based interventions and accommodations in the classroom for students who have sensory processing difficulties.

Mitochondrial Permeability Transition Dictates Mitochondrial Maturation Upon Switch In Cellular Identity Of Hematopoietic Precursors, Sandeep P Dumbali, Paulina D Horton, Travis I Moore, Pamela L Wenzel

Faculty, Staff and Student Publications

The mitochondrial permeability transition pore (mPTP) is a supramolecular channel that regulates exchange of solutes across cristae membranes, with executive roles in mitochondrial function and cell death. The contribution of the mPTP to normal physiology remains debated, although evidence implicates the mPTP in mitochondrial inner membrane remodeling in differentiating progenitor cells. Here, we demonstrate that strict control over mPTP conductance shapes metabolic machinery as cells transit toward hematopoietic identity. Cells undergoing the endothelial-to-hematopoietic transition (EHT) tightly control chief regulatory elements of the mPTP. During EHT, maturing arterial endothelium restricts mPTP activity just prior to hematopoietic commitment. After transition in cellular …

3d Chromatin Architecture, Brd4, And Mediator Have Distinct Roles In Regulating Genome-Wide Transcriptional Bursting And Gene Network, Pawel Trzaskoma, Seolkyoung Jung, Aleksandra Pękowska, Christopher H Bohrer, Xiang Wang, Faiza Naz, Stefania Dell'orso, Wendy D Dubois, Ana Olivera, Supriya V Vartak, Yongbing Zhao, Subhashree Nayak, Andrew Overmiller, Maria I Morasso, Vittorio Sartorelli, Daniel R Larson, Carson C Chow, Rafael Casellas, John J O'Shea

Faculty, Staff and Student Publications

Discontinuous transcription is evolutionarily conserved and a fundamental feature of gene regulation; yet, the exact mechanisms underlying transcriptional bursting are unresolved. Analyses of bursting transcriptome-wide have focused on the role of cis-regulatory elements, but other factors that regulate this process remain elusive. We applied mathematical modeling to single-cell RNA sequencing data to infer bursting dynamics transcriptome-wide under multiple conditions to identify possible molecular mechanisms. We found that Mediator complex subunit 26 (MED26) primarily regulates frequency, MYC regulates burst size, while cohesin and Bromodomain-containing protein 4 (BRD4) can modulate both. Despite comparable effects on RNA levels among these perturbations, acute depletion …

Rheumatoid Arthritis Disease Activity Is Associated With Frailty In Veterans, Courtney N. Loecker

Theses & Dissertations

Frailty, a physiologic vulnerability to everyday stressors, affects approximately 30% of the 1.3 million Americans with rheumatoid arthritis (RA) and is associated with increased risk for adverse health outcomes. Active RA manifests as inflammation, pain, and joint damage leading to functional impairments and morbidity which cumulatively influences frailty. However, the relationship between RA disease activity and frailty is incompletely understood.

This study evaluated the relationship of RA disease activity and frailty at baseline and over up to five years in Veterans. A cohort study was performed using data from the Veterans Affairs Rheumatoid Arthritis registry. RA disease activity was measured …

Improved Robustness For Deep Learning-Based Segmentation Of Multi-Center Myocardial Perfusion Mri Datasets Using Data Adaptive Uncertainty-Guided Space-Time Analysis., Dilek M Yalcinkaya, Khalid Youssef, Bobak Heydari, Janet Wei, Noel Bairey Merz, Robert Judd, Rohan Dharmakumar, Orlando P Simonetti, Jonathan W Weinsaft, Subha V Raman, Behzad Sharif

Heart and Vascular Articles

BACKGROUND: Fully automatic analysis of myocardial perfusion MRI datasets enables rapid and objective reporting of stress/rest studies in patients with suspected ischemic heart disease. Developing deep learning techniques that can analyze multi-center datasets despite limited training data and variations in software (pulse sequence) and hardware (scanner vendor) is an ongoing challenge.

METHODS: Datasets from 3 medical centers acquired at 3T (n = 150 subjects; 21,150 first-pass images) were included: an internal dataset (inD; n = 95) and two external datasets (exDs; n = 55) used for evaluating the robustness of the trained deep neural network (DNN) models against differences in …

The Impact Of Bariatric Surgery On Glutathione Synthesis In Individuals With Severe Obesity, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

Glycine is deficient in individuals with obesity but improves following bariatric surgery. Glycine deficiency could impair glutathione (GSH) synthesis and worsen oxidative stress. We examined the impact of obesity-associated glycine deficiency and bariatric surgery on GSH synthesis. Twenty-one participants with severe obesity and twenty-one healthy weight controls were recruited. [1,2-13C2] glycine was infused to measure the erythrocyte (RBC) GSH synthesis rate. Participants with obesity underwent bariatric surgery, and 19 were restudied six months post-surgery. Compared to healthy weight controls, individuals with obesity had significantly lower concentrations of RBC GSH (2.43 ± 0.23 vs. 2.63 ± 0.26 mmol/L, p < 0.01). However, there were no differences in GSH fractional synthesis rate [78.0 (51.4–123.7) vs. 76.9 (49.3–110.1) % pool/day, p = …

Single Cell Dual-Omic Atlas Of The Human Developing Retina, Zhen Zuo, Xuesen Cheng, Salma Ferdous, Jianming Shao, Jin Li, Yourong Bao, Jean Li, Jiaxiong Lu, Antonio Jacobo Lopez, Juliette Wohlschlegel, Aric Prieve, Mervyn G Thomas, Thomas A Reh, Yumei Li, Ala Moshiri, Rui Chen

Faculty, Staff and Students Publications

The development of the retina is under tight temporal and spatial control. To gain insights into the molecular basis of this process, we generate a single-nuclei dual-omic atlas of the human developing retina with approximately 220,000 nuclei from 14 human embryos and fetuses aged between 8 and 23-weeks post-conception with matched macular and peripheral tissues. This atlas captures all major cell classes in the retina, along with a large proportion of progenitors and cell-type-specific precursors. Cell trajectory analysis reveals a transition from continuous progression in early progenitors to a hierarchical development during the later stages of cell type specification. Both …

Proximity Analysis Of Native Proteomes Reveals Phenotypic Modifiers In A Mouse Model Of Autism And Related Neurodevelopmental Conditions, Yudong Gao, Daichi Shonai, Matthew Trn, Jieqing Zhao, Erik J Soderblom, S Alexandra Garcia-Moreno, Charles A Gersbach, William C Wetsel, Geraldine Dawson, Dmitry Velmeshev, Yong-Hui Jiang, Laura G Sloofman, Joseph D Buxbaum, Scott H Soderling

Faculty, Staff and Students Publications

One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-confidence autism risk genes within the mouse brain for proximity-based endogenous proteomics, achieving the identification of high-specificity spatial proteomes. The resulting native proximity proteomes are enriched for human genes dysregulated in the brain of autistic individuals, and reveal proximity interactions between proteins from high-confidence risk genes with those of lower-confidence that may provide new avenues to prioritize genetic risk. Importantly, the datasets are enriched for …

Left Atrial Venoarterial Extracorporeal Membrane Oxygenation Strategy In Postcardiotomy Cardiogenic Shock: A Case Series, Daniel Manzur-Sandoval Md, Gian Manuel Jiménez-Rodríguez Md, José Luis Elizalde-Silva Md, Meredith Fernanda Sánchez-Torres Md, Uriel Encarnación-Martínez Md, Cristhian Josué Gaytán-García Md, José Octavio Salazar-Delgado Md, Guadalupe Lisseth Hernández-González Md, Gustavo Rojas-Velasco Md

The VAD Journal

Postcardiotomy cardiogenic shock is a rare complication with high mortality. When patients do not respond to the placement of an intra-aortic balloon pump or pharmacological treatment, therapy with peripheral venoarterial extracorporeal membrane is a viable option that allows active resuscitation. The adjunct use of Impella® (Abiomed, Danvers, MA, USA) allows active unloading of the dysfunctional left ventricle. However, left atrial venoarterial extracorporeal membrane oxygenation (LAVA-ECMO) is an appealing and effective strategy in cases of aortic dissection, aortic valve replacement, or bioprosthesis of the aorta. Insertion of an extraction cannula that can discharge both atria or only the left atrium allows …

Examining The Impact Of Telehealth Visits On Patient And Family Experience In A Pediatric Emergency And Urgent Care Center, Abigail Gauthier Md, Callie Krentz Md, Shiran Chan Ms, Michelle Widecan Dnp, Aprn, Cpnp, Ac/Pc, Adam A. Vukovic Md, Med

Patient Experience Journal

Providers and healthcare organizations have created novel ways of evaluating patients using telehealth. Patient volumes in urgent cares (UCs) and emergency departments (EDs) continue to climb, contributing to longer wait times and suboptimal patient and family experiences (PFEs). Optimizing use of telehealth may not only impact PFE of those evaluated virtually, but also reduce crowding in EDs and UCs, indirectly impacting PFE in those spaces as well. The purpose of this study is to identify any association between telehealth encounters and PFE scores. This is a retrospective review of patients seen via telehealth in virtual urgent care, UC, or the …

Anti-Cdk Inhibitors For Cancer Treatment, Venkata M. Yenugonda

Technology Transfer - Patents

No abstract provided.

"I Just Assumed This Was Already Being Done": Canadian Patient Preferences For Enhanced Data Sharing For Precision Oncology, Samantha Pollard Pollard, Morgan Ehman, Anna Hermansen, Deirdre Weymann, Emanuel Krebs, Cheryl Ho, Howard J. Lim, Steven Jones, Yvonne Bombard, Tania M. Bubela

Office of the Provost

Purpose: In Canada, health data are siloed, slowing bioinnovation and evidence generation for personalized cancer care. Secured data-sharing platforms (SDSPs) can enable data analysis across silos through rapid concatenation across trial and real-world settings and timely researcher access. To motivate patient participation and trust in research, it is critical to ensure that SDSP design and oversight align with patients' values and address their concerns. We sought to qualitatively characterize patient preferences for the design of a pan-Canadian SDSP.
Methods: Between January 2022 and July 2023, we conducted pan-Canadian virtual focus groups with individuals who had a personal history of cancer. …

Sedation For Gi Endoscopy In The Morbidly Obese: Challenges And Possible Solutions, Lalitha Sundararaman, Basavana Goudra

Department of Anesthesiology Faculty Papers

With the increasing prevalence of obesity and morbid obesity, this subgroup's contribution to patients presenting for elective procedures requiring sedation is significant. Gastrointestinal (GI) procedures clearly form the largest group of such procedures. These procedures may be intended to treat obesity such as the insertion of an intragastric balloon or one or more unrelated procedures such as a screening colonoscopy and (or) diagnostic/therapeutic endoscopy. Regardless of the procedure, these patients pose significant challenges in terms of choice of sedatives, dosing, airway management, ventilation, and oxygenation. An understanding of dissimilarity in the handling of different groups of medications used by an …

Syphilitic Gumma Presenting As Squamous Cell Carcinoma Of Vulva: A Case Report, R.M. Nuss, A.J. Lazenby, Holly C. Provost, Tara Castellano

School of Medicine Faculty Publications

Introduction: Tertiary syphilis, a late form of the disease with neurologic, cutaneous, and cardiovascular manifestations, is rarely seen in the United States in modern times. Also called the “great imitator,” syphilis tends to mimic other disease processes, which can lead to a delay in proper diagnosis and treatment. Case: We present the case of a 59-year-old woman who presented for evaluation of possible squamous cell carcinoma of the vulva. After multiple inconclusive biopsies and extensive workup with multiple providers, she was instead found to have cutaneous and neurologic tertiary syphilis. A correct diagnosis was delayed in this patient due to …

Emerging Role Of Mucins In Antibody Drug Conjugates For Ovarian Cancer Therapy, Shabnam Malik, Mohammed Sikander, Natasha Bell, Daniel Zubieta, Maria C. Bell, Murali Yallapu, Subhash Chauhan

School of Medicine Publications

Ovarian cancer stands as the deadliest gynecologic malignancy, responsible for nearly 65% of all gynecologic cancer-related deaths. The challenges in early detection and diagnosis, coupled with the widespread intraperitoneal spread of cancer cells and resistance to chemotherapy, contribute significantly to the high mortality rate of this disease. Due to the absence of specific symptoms and the lack of effective screening methods, most ovarian cancer cases are diagnosed at advanced stages. While chemotherapy is a common treatment, it often leads to tumor recurrence, necessitating further interventions. In recent years, antibody-drug conjugates (ADCs) have emerged as a valuable tool in targeted cancer …

The Use Of Near-Infrared Angiography In Evaluating Bowel Anastomosis During A Gynecologic Oncology Surgery, Lea A. Moukarzel, Sarah Andres, Oliver Zivanovic

Abington Jefferson Health Papers

Reducing anastomotic leak rates after bowel resection is a priority among patients undergoing gynecologic oncology surgery. While near-infrared (NIR) angiography has been investigated in the colorectal literature, more recent work has demonstrated promising results when used in gynecologic cancer surgery. It has been repeatedly shown to be a safe intervention that can offer real time assessment of bowel perfusion, offering the surgeon the opportunity to act on the results in the hopes of decreasing the risk of complications.

Loss Of Transient Receptor Potential Channel 5 Causes Obesity And Postpartum Depression, Yongxiang Li, Tessa M Cacciottolo, Na Yin, Yang He, Hesong Liu, Hailan Liu, Yuxue Yang, Elana Henning, Julia M Keogh, Katherine Lawler, Edson Mendes De Oliveira, Eugene J Gardner, Katherine A Kentistou, Panayiotis Laouris, Rebecca Bounds, Ken K Ong, John R B Perry, Inês Barroso, Longlong Tu, Jonathan C Bean, Meng Yu, Kristine M Conde, Mengjie Wang, Olivia Ginnard, Xing Fang, Lydia Tong, Junying Han, Tia Darwich, Kevin W Williams, Yongjie Yang, Chunmei Wang, Shelagh Joss, Helen V Firth, Yong Xu, I Sadaf Farooqi

Duncan NRI Faculty and Staff Publications

Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain. Male TRPC5 deletion carriers exhibited food seeking, obesity, anxiety, and autism, which were recapitulated in knockin male mice harboring a human loss-of-function TRPC5 mutation. Women carrying TRPC5 deletions had severe postpartum depression. As mothers, female knockin mice exhibited anhedonia and depression-like behavior with impaired care of offspring. Deletion of …

Translational Potential Of Mouse Models Of Human Metabolic Disease, I Sadaf Farooqi, Yong Xu

Children’s Nutrition Research Center Staff Publications

Obesity causes significant morbidity and mortality globally. Research in the last three decades has delivered a step-change in our understanding of the fundamental mechanisms that regulate energy homeostasis, building on foundational discoveries in mouse models of metabolic disease. However, not all findings made in rodents have translated to humans, hampering drug discovery in this field. Here, we review how studies in mice and humans have informed our current framework for understanding energy homeostasis, discuss their challenges and limitations, and offer a perspective on how human studies may play an increasingly important role in the discovery of disease mechanisms and identification …

Changing Landscape Of Liver Transplant In The United States—Time For A New Innovative Way To Define And Utilize The “Non-Standard Liver Allograft”—A Proposal, Rashmi Seth, Kenneth Andreoni

Department of Surgery Faculty Papers

Since the first liver transplant was performed over six decades ago, the landscape of liver transplantation in the US has seen dramatic evolution. Numerous advancements in perioperative and operative techniques have resulted in major improvements in graft and patient survival rates. Despite the increase in transplants performed over the years, the waitlist mortality rate continues to remain high. The obesity epidemic and the resultant metabolic sequelae continue to result in more marginal donors and challenging recipients. In this review, we aim to highlight the changing characteristics of liver transplant recipients and liver allograft donors. We focus on issues relevant in …

Novel Il-4/Hb-Egf-Dependent Crosstalk Between Eosinophils And Macrophages Controls Liver Regeneration After Ischaemia And Reperfusion Injury, Yang Yang, Long Xu, Constance Atkins, Lily Kuhlman, Jie Zhao, Jong-Min Jeong, Yankai Wen, Nicolas Moreno, Kang Ho Kim, Yu A An, Fenfen Wang, Steve Bynon, Vincenzo Villani, Bin Gao, Frank Brombacher, Raymond Harris, Holger K Eltzschig, Elizabeth Jacobsen, Cynthia Ju

Faculty, Staff and Student Publications

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair.

DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding …

The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton

Faculty, Staff and Students Publications

Structural variation heavily influences the molecular landscape of cancer, in part by impacting DNA methylation-mediated transcriptional regulation. Here, using multi-omic datasets involving >2400 pediatric brain and central nervous system tumors of diverse histologies from the Children's Brain Tumor Network, we report hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of somatic structural variant (SV) breakpoints is recurrently associated with altered expression or DNA methylation, respectively, including tumor suppressor genes ATRX and CDKN2A. Altered DNA methylation near enhancers associates with nearby somatic SV breakpoints, including MYC and MYCN. A subset of genes with SV-CGI methylation associations …

Lysineless Hibit And Nanoluc Tagging Systems As Alternative Tools For Monitoring Targeted Protein Degradation, Hanfeng Lin, Kristin Riching, May Poh Lai, Dong Lu, Ran Cheng, Xiaoli Qi, Jin Wang

Faculty, Staff and Students Publications

Target protein degradation (TPD) has emerged as a revolutionary approach in drug discovery, leveraging the cell’s intrinsic machinery to selectively degrade disease-associated proteins. Nanoluciferase (nLuc) fusion proteins and the NanoBiT technology offer two robust and sensitive screening platforms to monitor the subtle changes in protein abundance induced by TPD molecules. Despite these advantages, concerns have arisen regarding potential degradation artifacts introduced by tagging systems due to the presence of lysine residues on them, prompting the development of alternative tools. In this study, we introduce HiBiT-RR and nLucK0, variants devoid of lysine residues, to mitigate such artifacts. Our findings demonstrate that …

Pan-Cancer Proteogenomics Expands The Landscape Of Therapeutic Targets, Sara R Savage, Xinpei Yi, Jonathan T Lei, Bo Wen, Hongwei Zhao, Yuxing Liao, Eric J Jaehnig, Lauren K Somes, Paul W Shafer, Tobie D Lee, Zile Fu, Yongchao Dou, Zhiao Shi, Daming Gao, Valentina Hoyos, Qiang Gao, Bing Zhang

Faculty, Staff and Students Publications

Fewer than 200 proteins are targeted by cancer drugs approved by the Food and Drug Administration (FDA). We integrate Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomics data from 1,043 patients across 10 cancer types with additional public datasets to identify potential therapeutic targets. Pan-cancer analysis of 2,863 druggable proteins reveals a wide abundance range and identifies biological factors that affect mRNA-protein correlation. Integration of proteomic data from tumors and genetic screen data from cell lines identifies protein overexpression- or hyperactivation-driven druggable dependencies, enabling accurate predictions of effective drug targets. Proteogenomic identification of synthetic lethality provides a strategy to target tumor …