Digestive System Diseases Commons^™

Atypical Presentation Of Acute Appendicitis: A Case Report, Yudhistira Pradnyan Kloping, R. Cita Resti Anantia Putri

The New Ropanasuri Journal of Surgery

Despite the fact that acute appendicitis is one of the most common surgical emergencies worldwide, delays in establishing a diagnosis still occur. We report a case of acute appendicitis with an atypical presentation based on the patient’s clinical and laboratory findings. A 25-year-old male was brought with pain in his right lower quadrant. Pain migration, fever, anorexia, nausea, vomiting, or dysuria were denied. Laboratory results were within normal limits. USG examination was not able to visualize the appendix. An abdominal CT-Scan showed a sign of acute appendicitis. The patient was planned for appendectomy. It is important to not immediately rule …

Efficacy Of Fecal Microbiota Transplant In Conjunction With Oral Vancomycin For The Treatment Of Recurrent Clostridium Difficile, Abigayle Afflick, Jackson Laboue

Physician Assistant Capstones, 2020-current

Objective: To determine the effectiveness of fecal microbiota transplant in addition to traditional therapy of oral vancomycin for the treatment of recurrent Clostridium difficile infections. Methods: Google Scholar was searched to identify randomized control trials using the terms vancomycin, fecal transplant, c. diff, and recurrent. Results: Three studies met inclusion criteria and two found a statistically significant benefit to the addition of fecal microbiota transplant to vancomycin therapy. Cammarota, et al. reported a 90% cure rate when administering fecal microbiota transplant in addition to vancomycin as opposed to a 26% cure rate with vancomycin alone with a P value …

Dysphagia And Masticatory Performance As A Mediator Of The Xerostomia To Quality Of Life Relation In The Older Population., Ting-Yu Lu, Jen-Hao Chen, Je-Kang Du, Ying-Chun Lin, Pei-Shan Ho, Chien-Hung Lee, Chih-Yang Hu, Hsiao-Ling Huang

School of Public Health Faculty Publications

Background: The impact of poor oral health on older adults' quality of life is a public health problem. In this study, the mediating effects of dental status, occlusal condition, dysphagia, and masticatory performance on the association between xerostomia and oral health-related quality of life (OHRQoL) were assessed in the older adult population.Methods: Stratified cluster sampling was used to recruit 1076 community-dwelling adults aged 65 years and older from Kaohsiung, Taiwan. Community care centers were randomly selected according to their geographic classifications (urban, rural, or mountainous areas). Assessments of dental status and occlusal condition were performed by dentists. Information on demographics, …

The Role Of Liver Sinusoidal Endothelial Cells In Liver Malady Homeostasis, Fatima Cabral

Department of Biochemistry: Dissertations, Theses, and Student Research

Current literature described techniques for the purification of liver cell types through text alone. The techniques described for the isolation of liver sinusoidal endothelial cells as well as hepatocytes described here are modified from a published article in the Journal of Visualized experiments. The video protocol allows for the user to successfully isolate cells as the most difficult parts of the procedure are demonstrated visually. The detection of liver maladies such as the non-alcoholic fatty liver disease, the stage if this disease and differentiation between non-alcoholic and alcoholic fatty liver disease is demonstrated in the development of a unique panel …

Model For End-Stage Liver Disease-Sodium Underestimates 90-Day Mortality Risk In Patients With Acute-On-Chronic Liver Failure, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Abbas Rana, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: It is unclear whether the model for end-stage liver disease-sodium (MELD-Na) score captures the clinical severity of acute-on-chronic liver failure (ACLF). We compared observed 90-day mortality in patients with ACLF with expected mortality based on the calculated MELD-Na and examined the consequences of underestimating clinical severity.

METHODS: We identified patients with ACLF during hospitalization for cirrhosis in 127 VA hospitals between 01/01/2004 and 12/31/2014. We examined MELD-Na scores by ACLF presence and grade. We used actual and observed 90-day mortality to estimate a standardized mortality ratio (SMR) by ACLF presence and grade. We used transplant center-specific median …

In Silico Modelling For The Treatment Of Gastric Cancer, Leonardo F. Martinez, Diana Gamboa, Paul A. Valle

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Exploring Peer Mentoring In Pediatric Transition: Perspectives Of Different Stakeholders About Accompanying Patients In Gastroenterology, Guillaume Dumais-Lévesque, Marie-Pascale Pomey

Patient Experience Journal

The literature identifies several issues in the pediatric transition, such as the lack of coordination between pediatric and adult settings and young patients who are not exercising independence in the self-management of their disease. The objective of this study is to explore the potential for a pediatric transition program in gastroenterology, introducing an accompanying patient program to support the transition. A qualitative case study was conducted, including semi-structured focus groups and individual interviews with each group involved in the pediatric transition between two centres in Quebec. A thematic analysis of the collected data was performed using QDA Miner v5.1. In …

Associations Between Household-Level Exposures And All-Cause Diarrhea And Pathogen-Specific Enteric Infections In Children Enrolled In Five Sentinel Surveillance Studies, Josh M. Colston, Abu S G. Faruque, M Jahangir Hossain, Debasish Saha, Suman Kanungo, Inácio Mandomando, Muhammad Imran Nisar, Anita K. M. Zaidi, Richard Omore, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Diarrheal disease remains a major cause of childhood mortality and morbidity causing poor health and economic outcomes. In low-resource settings, young children are exposed to numerous risk factors for enteric pathogen transmission within their dwellings, though the relative importance of different transmission pathways varies by pathogen species. The objective of this analysis was to model associations between five household-level risk factors-water, sanitation, flooring, caregiver education, and crowding-and infection status for endemic enteric pathogens in children in five surveillance studies. Data were combined from 22 sites in which a total of 58,000 stool samples were tested for 16 specific enteropathogens using …

Investigating Microbial And Host Factors That Modulate Severity Of Clostridioides Difficile Associated Disease, Armando Lerma

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Clostridioides difficile is recognized as one of the most important pathogens in hospital and community healthcare settings. The clinical outcome of infection of toxigenic C. difficile infection (CDI) ranges from asymptomatic colonization to fulminant pseudomembranous colitis and death. In recent studies, it has been suggested that a high proportion of nosocomial CDI cases are transmitted from asymptomatic carriers which might be acting as infection reservoirs. Understanding what causes the different responses to infection could lead to the development of novel prevention and treatment strategies. Although several explanations have been proposed to explain variations in susceptibility, understanding of the exact mechanisms …

A Case Of Plesiomonas Bacteremia Without Reported Freshwater Exposure, Abigail E. Mcdonald

HCA Healthcare Journal of Medicine

Introduction: Plesiomonas shigelloides is a member of the Enterobacteriaceae family generally found in freshwater. There is little substantive data about the prevalence or distribution of Plesiomonas within the United States. Plesiomonas are most commonly associated with mild, self-limited watery diarrhea among healthy individuals followed by infective colitis. Bacteremia is the most common extraintestinal manifestation of Plesiomonas. Few cases of Plesiomonas bacteremia can be found in the literature.

Clinical Findings: An elderly female with multiple comorbidities was admitted to our hospital for evaluation of generalized cramping abdominal pain of several days duration. She denied any freshwater or saltwater exposure. The …

Risk Prediction Rule For Advanced Neoplasia On Screening Colonoscopy For Average-Risk Individuals, Ala I Sharara, Ali El Mokahal, Ali H Harb, Natalia Khalaf, Fayez S Sarkis, Mustapha M El-Halabi, Nabil M Mansour, Ahmad Malli, Robert Habib

Faculty, Staff and Students Publications

BACKGROUND: In resource-limited countries, risk stratification can be used to optimize colorectal cancer screening. Few prospective risk prediction models exist for advanced neoplasia (AN) in true average-risk individuals.

AIM: To create and internally validate a risk prediction model for detection of AN in average-risk individuals.

METHODS: Prospective study of asymptomatic individuals undergoing first screening colonoscopy. Detailed characteristics including diet, exercise and medications were collected. Multivariate logistic regression was used to elucidate risk factors for AN (adenoma ≥1 cm, villous histology, high-grade dysplasia or carcinoma). The model was validated through bootstrapping, and discrimination and calibration of the model were assessed.

RESULTS: …

Gastrointestinal Symptoms In Patients With Covid-19, Mohammed Abbas, Rafik Elbeblawy, Islam Gadelmoula, Suvarna Rekha, Bettina Sinanova, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Introduction: Though coronavirus disease 2019 (COVID-19) is predominantly a respiratory illness, a growing number of studies reported gastrointestinal (GI) symptoms among these patients. We examined the incidence of GI symptoms in patients with COVID-19 and GI symptoms as the initial presentation of the disease.

Methods: We examined peer-reviewed studies in English of patients with COVID-19 that reported GI symptoms. We searched PubMed and Google Scholar for articles published up to June 30, 2020, by using the keywords ``COVID-19,'' ``Coronavirus,'' ``severe acute respiratory syndrome coronavirus 2,'', ``SARS-CoV-2,'' ``gastrointestinal tract,'' ``gastrointestinal diseases,'' and ``gastrointestinal symptoms and signs.'' Studies with fewer than 30 …

Laryngeal Histoplasmosis In Patients With Crohn’S Disease Undergoing Treatment With Humira (Adalimumab): A Case Series, Jenna Berg, Jonathan Blecha, Chris Bingcang, Justin Oltman, Jayme Dowdall, Subodh M. Lele

Graduate Medical Education Research Journal

The FDA has advocated for increasing awareness of histoplasmosis for patients undergoing TNF blockers as delay in diagnosis can lead to a poor outcome.¹ Laryngeal histoplasmosis is a rare entity that should be part of the differential diagnosis in patients receiving immune suppression for Crohn’s disease. Patients with laryngeal histoplasmosis often report hoarseness, mucosal ulcerations, dysphagia, and odynophagia. We present a series of two cases of laryngeal histoplasmosis in patients with Crohn’s. These cases illustrate the high index of suspicion required to make the diagnosis of laryngeal histoplasmosis, especially in the Midwestern United States. Diagnosis is made quickly and …

Clinical Efficacy Of Direct-Acting Antiviral Therapy For Recurrent Hepatitis C Virus Infection After Liver Transplantation In Patients With Hepatocellular Carcinoma, Mohamed Saleh Ismail, Manal Hassan, Saira Aijaz Khaderi, Wael Ahmed Yousry, Maha Mohsen Kamal El-Din, Mohamed Mohamed Bahaa El-Din, Osama Aboelfotoh El Sayed, Ahmed Omar Kaseb, John Alan Goss, Fasiha Kanwal, Prasun Kumar Jalal

Faculty, Staff and Students Publications

BACKGROUND: Recurrent hepatitis C virus (HCV) infection of transplanted liver allografts is universal in patients with detectable HCV viremia at the time of transplantation. Direct-acting antiviral (DAA) therapy has been adopted as the standard of care for recurrent HCV infection in the post-transplant setting. However, there are insufficient data regarding its efficacy in liver transplant (LT) recipients with a history of hepatocellular carcinoma (HCC), and the risk of HCC recurrence after DAA therapy is unknown.

AIM: To demonstrate predictors of DAA treatment failure and HCC recurrence in LT recipients.

METHODS: A total of 106 LT recipients given DAAs for recurrent …

Structural Characterization Of A Clinically Described Heparin-Like Substance In Plasma Causing Bleeding, Yanlei Yu, Karen Bruzdoski, Vadim Kostousov, Lisa Hensch, Shiu-Ki Hui, Fakiha Siddiqui, Amber Farooqui, Ahmed Kouta, Fuming Zhang, Jawed Fareed, Jun Teruya, Robert J Linhardt

Faculty, Staff and Students Publications

Heparin-like substances (HLS) have been described in various clinical situations, including in settings of liver disease associated with infection, transplant, and metastasis. HLS are generally attributed to circulating glycosaminoglycans. Initial results for this patient showed coagulopathy due to liver disease without HLS. Two weeks after liver transplantation, a 10 year-old female with liver failure patient began to bleed from catheter insertion sites, mouth, and nares and HLS was suspected. The patient subsequently died and these clinical samples resulted in the isolation of a single heparan sulfate (HS) present at high concentrations in the plasma. Analysis of this HS showed it …

Early Transplantation In Acute On Chronic Liver Failure: Who And When, Nadim Mahmud, Ruben Hernaez, Tiffany Wu, Vinay Sundaram

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Acute on chronic liver failure (ACLF) is a unique syndrome that afflicts patients with chronic liver disease and results in high short-term mortality, > 50% at 28 days in patients with severe ACLF (grade 3, ACLF-3). Given this prognosis, there is an urgent need to understand risk factors for this condition, as well as selection criteria for patients who may benefit from liver transplantation (LT).

RECENT FINDINGS: Several studies have identified risk factors for developing ACLF, including higher model for end-stage liver disease score, anemia, and morbid obesity, as well ACLF mortality, such as infection, increasing organ failures, …

Early Aggressive Hydration Is Associated With Decreased Opioid Use And Readmission In Mild Acute Pancreatitis, Shreyans Doshi, Hong Liang, Hale Z. Toklu, Selina Fritze, Sue-Wei Luu

HCA Healthcare Journal of Medicine

Background: Acute pancreatitis (AP) is one of the most common causes of hospital admissions due to gastrointestinal disorders. No pharmacologic agents have been proven to impact the prognosis, and the treatment still remains supportive with intravenous fluids for hydration. Although early hydration has been recommended for the management of mild AP, there is no consensus on the type, rate, and amount of the fluid replacement.

Objective: In this study, we aimed to investigate the outcome of aggressive hydration in patients with AP.

Methods: Retrospective data from patients admitted to 12 hospitals (2015–2017) was used for analysis. Five hundred patients who …

A Policy Change To Reduce Hospital-Acquired Clostridium Difficile Infection Rates: A Quality Improvement Project, Nia Hidalgo

Student Scholarly Projects

Practice Problem: At a small community facility in Los Angeles County, there was a reporting rate of hospital-acquired Clostridium difficile cases that was higher than both state and national benchmarks.

PICOT: The PICOT question that guided this project was: In acute care patients aged 18-90, does not retesting for CDI for at least seven days compared to retesting in less than seven days reduce the incidence of false positive CDI tests during the first seven days of the hospital stay?

Evidence: The evidence demonstrates that if patients are tested initially for Clostridium difficile and then retested seven days after, the …

Low Anterior Resection Syndrome, Theresa H Nguyen, Reena V Chokshi

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Low anterior resection syndrome is a highly prevalent condition that can develop after anal sphincter-sparing surgery for rectal cancer and impair quality of life. In this review, we summarize the major features and pathophysiology of this syndrome and discuss treatment approaches.

RECENT FINDINGS: Quality of life correlates significantly with severity of low anterior resection syndrome. Prompt assessment and initiation of therapy are essential to rehabilitating damaged mechanical and neural structures. Anorectal manometry demonstrates a global decrease in sphincteric function postoperatively, though in many patients, function does recover. Transanal irrigation, pelvic floor rehabilitation, and biofeedback are the mainstays …

Post-Registration Experience Of Nivolumab In Advanced Hepatocellular Carcinoma: An International Study, Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, Chiehju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato

Faculty, Staff and Students Publications

BACKGROUND: Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.

PATIENTS AND METHODS: We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.

RESULTS: Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line …

Prevalence Of Helicobacter Pylori Positive Non-Cardia Gastric Adenocarcinoma Is Low And Decreasing In A Us Population, Theresa H Nguyen, Niharika Mallepally, Tariq Hammad, Yan Liu, Aaron P Thrift, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND: Helicobacter pylori infection is an established causal factor for non-cardia gastric cancer. H. pylori negative gastric cancer prevalence among US patients is unclear.

METHODS: This retrospective cohort study examined H. pylori prevalence among consecutive patients with incident non-cardia gastric adenocarcinoma at the Houston VA Hospital (11/2007-10/2018). H. pylori positivity was defined by H. pylori on histopathology, positive antibody serology, stool antigen, or urea breath testing. We examined for trends in H. pylori negative gastric cancer based on year of diagnosis. Associations between histopathologic and cancer-related outcomes with H. pylori positivity were determined using regression models.

RESULTS: Of 91 patients …

Chronic Abdominal Pain In A Geriatric Patient: A Rare Case Of A Spigelian Hernia, Thomas D. Wright, Olumayowa Dayo, Lynne J. Goebel

Marshall Journal of Medicine

We present a case of Spigelian hernia in a 77-year-old patient to highlight the difficulty in making this diagnosis and to raise awareness of this rare condition among physicians who care for geriatric patients with chronic bouts of abdominal pain. The patient presented to the emergency department with a two-day complaint of abdominal pain after three years of similar recurrent attacks. Results of the physical examination and computed tomography (CT) of the abdomen were consistent with a left-sided Spigelian hernia. Operative repair was performed using robotic-assisted reduction and the patient recovered without any complications.

Immunotherapy In Hepatocellular Cancer Patients With Mild To Severe Liver Dysfunction: Adjunctive Role Of The Albi Grade, David J Pinato, Takahiro Kaneko, Anwaar Saeed, Tiziana Pressiani, Ahmed Kaseb, Yinghong Wang, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Chieh-Ju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I Abugabal, Celina Ang, Thomas U Marron, Uqba Khan, Nicola Personeni, Lorenza Rimassa, Yi-Hsiang Huang

Faculty, Staff and Students Publications

Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied …

Low Yield Of Hepatitis C Infection In An Outreach Screening Program In Harris County, Texas, Hyun-Seok Kim, Rosalia Guerrero, Shane W Reader, Maria Daheri, Maya Balakrishnan, Catherine L Troisi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

A community outreach hepatitis C virus (HCV) infection screening program provided low yield of detecting HCV-infected patients, linking them to our hepatology clinic for treatment. Our data underscore that most of the yield was related to addiction centers and birth cohort; these groups should be targeted by future interventions.

Impact Of Covid-19 On Pediatric Gastroenterology Fellow Training In North America, Daniel Mallon, John F Pohl, Uma P Phatak, Melissa Fernandes, John M Rosen, Sarah S Lusman, Cade M Nylund, Candi S Jump, Aliza B Solomon, Arvind Srinath, Andrew Singer, Rula Harb, Norberto Rodriguez-Baez, Kristin L Whitfield Van Buren, Shifra Koyfman, Riha Bhatt, Dellys M Soler-Rodriguez, Mamata Sivagnanam, Christine K Lee, Naspghan Training Committee Covid-19 Survey Working Group

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training.

METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics.

RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to …

Renal Trajectory Patterns Are Associated With Postdischarge Mortality In Patients With Cirrhosis And Acute Kidney Injury, Ayse L Mindikoglu, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Thomas Taylor, Abbas Rana, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Little is known about long-term outcomes of acute kidney injury (AKI) in patients with cirrhosis. Outcomes can vary with stage of AKI, chronic kidney disease, and trajectory of renal function.

METHODS: We collected data from the Department of Veterans Affairs and identified 6917 patients with cirrhosis who developed AKI during hospitalization at any of its 127 hospitals, from 2004 through 2014. We used latent class analysis of serial creatinine measurements during the index hospitalization to determine trajectories of renal function.

RESULTS: Overall, 32% of patients died within 90 days of discharge from the hospital and 48% of …

Systemic Proteome Alterations Linked To Early Stage Pancreatic Cancer In Diabetic Patients, Hong Peng, Sheng Pan, Yuanqing Yan, Randall E Brand, Gloria M Petersen, Suresh T Chari, Lisa A Lai, Jimmy K Eng, Teresa A Brentnall, Ru Chen

Faculty, Staff and Students Publications

BACKGROUND: Diabetes is a risk factor associated with pancreatic ductal adenocarcinoma (PDAC), and new adult-onset diabetes can be an early sign of pancreatic malignancy. Development of blood-based biomarkers to identify diabetic patients who warrant imaging tests for cancer detection may represent a realistic approach to facilitate earlier diagnosis of PDAC in a risk population.

METHODS: A spectral library-based proteomic platform was applied to interrogate biomarker candidates in plasma samples from clinically well-defined diabetic cohorts with and without PDAC. Random forest algorithm was used for prediction model building and receiver operating characteristic (ROC) curve analysis was applied to evaluate the prediction …

Facing Real-World Challenges Of Immunogenicity In Pediatric Inflammatory Bowel Disease., Kyle Gress, Julie A. Bass, Ryan S Funk, Ryan Morrow, Rachel Hasenkamp, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Internal Hernia As A Late Complication Of Roux-En-Y Gastric Bypass Procedure, Samantha Purton, Gabriel Meshekow, My Myers, Edgar Mercado, Allan Katz

West Florida Division GME Research Day 2020

As the prevalence of obesity continues to rise, so does the popularity of bariatric surgery. Previously the Roux-en-Y gastric bypass was the most common bariatric procedure, but now falls second to the gastric sleeve. It remains a relevant procedure, however, accounting for 17% of bariatric procedures in 2018. Due to its prevalence, it is important that the radiologist be familiar with the procedure and its complications such as leak, obstruction, stricture, or, as in this case, internal herniation through a mesenteric defect. Internal hernias are more commonly associated with the laparoscopic approach versus open. This is likely due to fewer …

Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray

Faculty, Staff and Students Publications

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool …