Digital Commons Network^™

Corrigendum To "Single-Cell Proteomic Analysis Reveals Multiple Myeloma Heterogeneity And The Dynamics Of The Tumor Immune Microenvironment In Precursor And Advanced States" [Neoplasia 66 (2025) 1101189], Mohamed Kamal, Stephanie N Shishido, Jeremy Mason, Krina Patel, Elisabet E Manasanch, Robert Z Orlowski, Peter Kuhn

Faculty, Staff and Student Publications

No abstract provided.

Meeting Report From The 2024 Symposium On Irak4 In Cancer: Highlights And Clinical Updates, Eric S Winer, Marina Konopleva, Han W Tun, Kian-Huat Lim, Bently Doonan, Klaus H Metzeler, Lakshmi Nayak, Andrés J M Ferreri, Christina Von Roemeling, Grzegorz S Nowakowski, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a serine/threonine kinase that mediates interleukin-1 and Toll-like receptor (TLR) signaling. IRAK4 drives the activation of nuclear factor kappa B (NF-κB), which promotes cell survival, inflammation, and proliferation. Aberrant activation of IRAK4 and TLR signaling has been implicated in multiple malignancies. At the 3rd Annual IRAK4 in Cancer Symposium, experts discussed the role of IRAK4 in cancer biology, the potential for synergism between IRAK4 inhibition and other treatments to overcome resistance, and how IRAK4 inhibition may improve clinical outcomes. Preclinical data were presented demonstrating the activity of IRAK4 inhibition alone or in combination with …

Cardiovascular Multimorbidity In Older Adults In The United States By Race And Sex, Michael D Green, Robert J Mentz, Stephen J Greene, Bradley G Hammill, Utibe R Essien, Ying Xian, Erin D Michos, Roland J Thorpe, Matthew E Dupre, Brian Mac Grory, Chi-Tsun Chiu, Emily C O'Brien, Jay B Lusk

Faculty, Staff and Student Publications

Background: It is essential to understand the prevalence of cardiovascular multimorbidity and to recognize disparities by race and sex to promote health equity.

Objectives: The objectives of the study are to investigate disparities in the development and progression of cardiovascular multimorbidity among older adults in the United States and estimate relative life expectancies among patients with cardiovascular multimorbidity.

Methods: This was a nationwide study of a 5% nationwide sample of fee-for-service Medicare beneficiaries aged 65 or older from 2010 to 2020. Multistate survival models were employed to estimate cardiovascular disease (CVD) progression and a microsimulation approach was used to derive …

Misfolded Amyloid-Beta Conformational Variants (Strains) As Drivers Of Alzheimer's Disease Neuropathology, Salvatore Saieva, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

B-Cell-Specific Wwox Deletion Promotes Plasmablastic Tumor Development And Proinflammatory Signatures In Myeloma Model, Tabish Hussain, Matthew D Bramble, Bin Liu, Martin C Abba, Marta Chesi, C Marcelo Aldaz

Faculty, Staff and Student Publications

Deletions and translocations affecting WWOX accompanied by loss of expression are frequently observed in B-cell neoplasms and are linked to poor prognosis. Our previous research showed that Wwox deletion early in B-cell development induces genomic instability, neoplastic transformation, and monoclonal gammopathies in mice. In this study, by crossing Cd19 Wwox knockout (KO) with Vk^∗MYC myeloma model mice, we generated a model with concurrent Wwox deletion and MYC activation, reproducing 2 common oncogenic alterations in B- and plasma-cell cancers. We observed that Vk^∗MYC:Wwox KO mice exhibited significantly reduced survival rates primarily due to the development of plasmablastic …

Omacetaxine And Venetoclax In Relapsed/Refractory Acute Myeloid Leukemia Or Myelodysplastic Syndrome With Mutant Runx1, Courtney D Dinardo, Wei-Ying Jen, Guillermo Montalban-Bravo, Xuemei Wang, Sanam Loghavi, Sravanthi Lavu, Nicholas J Short, Kelly Chien, Ghayas C Issa, Naveen Pemmaraju, Musa Yilmaz, Michael Andreeff, Gautam Borthakur, Tapan M Kadia, Naval G Daver, Guillermo Garcia-Manero, Christopher P Mill, Xiaoping Su, Warren Fiskus, Kapil N Bhalla

Faculty, Staff and Student Publications

Mutations in RUNX1 (RUNX1mut) occur in 10% to 20% of patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and are associated with poor outcomes to standard therapy. Omacetaxine mepesuccinate (OM), a semisynthetic analog of homoharringtonine, has been shown to be lethal to RUNX1mut AML cells in vitro through reduction of MCL1 and BCL-XL, and synergizes with venetoclax (VEN) in RUNX1mut AML models. We investigated the safety and efficacy of OM + VEN in relapsed/refractory RUNX1mut MDS/AML in a Bayesian Optimal Interval design. VEN 400 mg daily from days 1 to 14 and OM …

Inhibition Of Bmper Mitigates Pulmonary Hypertension By Modulating Lrp1-Yap Interaction In Smooth Muscle Cells, Hua Mao, Claire M Li, Bing Sun, Christopher S Ward, Alan R Waich-Cohen, Ivan O Rosas, Howard J Huang, Harry Karmouty-Quintana, Liang Xie, Lavannya M Pandit, Xinchun Pi

Faculty, Staff and Students Publications

Background: BMPER (bone morphogenetic protein-binding endothelial regulator) is a secreted protein that is highly expressed in endothelial cells. It regulates the BMP (bone morphogenetic protein) pathway during vascular development and adulthood. Mutations in the BMP pathway are recognized as risk factors for pulmonary arterial hypertension group 1 pulmonary hypertension (PH). However, the roles of BMPER in pulmonary arterial hypertension remain unknown.

Methods: We assessed BMPER expression in Group 1 pulmonary arterial hypertension patient samples and examined its role in vascular remodeling using in vivo and in vitro approaches.

Results: BMPER level was elevated in pulmonary arterial hypertension lungs and significantly …

High Risk Of Persistence And Risk Of Dysplasia After Diagnosis Of Ultrashort Barrett's Esophagus, Wasseem Skef, Jasmine Haydel, Ashwin Rao, Ronan Allencherril, Rollin George, Gyanprakash A Ketwaroo, Aaron P Thrift, Hashem B El-Serag, Theresa Nguyen Wenker

Faculty, Staff and Students Publications

Introduction: The management of ultrashort (< 1 cm) Barrett's esophagus (BE) remains unclear. We aimed to determine the prevalence of ultrashort BE (USBE) at index diagnosis, identify factors associated with persistent BE after USBE diagnosis, and identify risk of dysplasia after initial USBE in a population of US veterans.

Methods: This was a retrospective cohort study at the Veterans Affairs hospital in Houston, TX, of consecutive patients with new BE diagnosis from November 1990 to June 2022 with follow-up through April 2023. Using a pathology database, we identified patients with a new USBE diagnosis and any subsequent follow-up esophagogastroduodenoscopy (EGD). We examined the association of sociodemographic and clinical risk factors of persistent USBE cohort compared with longer-length segment BE and those with a negative follow-up EGD after index USBE with χ 2 tests and logistic regression models. Last, we calculated the prevalence and …

Hand Swelling And Other Non-Raynaud Phenomenon Symptoms As The Initial Presentation Of Systemic Sclerosis: Prevalence And Clinical Associations In Two Us Cohorts, Iqtidar Hanif, Shervin Assassi, Maureen D Mayes, Zsuzsanna H Mcmahan, Meng Zhang, Julio Charles, John M Vanburen, Jessica S Alvey, Kimia Ghaffari, Elana J Bernstein, Flavia V Castelino, Lorinda Chung, Luke Evnin, Tracy M Frech, Jessica K Gordon, Faye N Hant, Laura K Hummers, Dinesh Khanna, Kimberly S Lakin, Dorota Lebiedz-Odrobina, Yiming Luo, Ashima Makol, Jerry A Molitor, Duncan F Moore, Carrie Richardson, Nora Sandorfi, Ami A Shah, Ankoor Shah, Victoria K Shanmugam, Virginia D Steen, Elizabeth R Volkmann, Carleigh Zahn, Brian Skaug

Faculty, Staff and Student Publications

Objective: Raynaud phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts.

Methods: All patient data in the Genetics vs Environment in Scleroderma Outcomes Study (GENISOS) and Collaborative National Quality and Efficacy Registry (CONQUER) cohorts were reviewed. Both studies enrolled patients within five years of the first non-RP symptom.

Results: In GENISOS and CONQUER, respectively, 194 (44.2%) of 439 and 292 …

Acute And Chronic Nasal Inflammation Induces Lymphangiogenesis In The Olfactory Mucosa In Mice, Suzuho Komaki, Ryuichi Imai, Yuzuki Sugimoto, Rei Settsu, Aki Obara, Atsuyoshi Shimada, Robert Dantzer, Geoffroy Laumet, Fumiaki Imamura, Sanae Hasegawa-Ishii

Faculty, Staff and Student Publications

Background: Lymphangiogenesis, the formation of new lymphatic vessels, is primarily driven by VEGF-C-mediated activation of VEGFR-3 and plays a critical role in immune regulation and tissue repair. Although lymphangiogenesis has been well documented in various inflamed tissues, its occurrence and spatiotemporal characteristics in the olfactory mucosa during nasal inflammation remain poorly understood. To address this, we investigated the localization and development of lymphatic vessels in a mouse model of both acute and chronic nasal inflammation.

Methods: Acute inflammation was induced by intranasal administration of lipopolysaccharide (LPS; 10 μg per nostril) in 8-week-old male mice, with saline-treated mice as controls. Behavioral …

Outcomes And Patterns Of Relapse Of Npm1 Mutated Acute Myeloid Leukemia Treated With Venetoclax Based Therapies, Wei-Ying Jen, Sanam Loghavi, Alexandre Bazinet, Alex Bataller, Ian Bouligny, Naval G Daver, Ghayas C Issa, Naszrin Arani, Emmanuel Almanza Huante, Abhishek Maiti, Guillermo Montalban-Bravo, Gautam Borthakur, Nicholas J Short, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi, Hagop M Kantarjian, Courtney D Dinardo, Tapan M Kadia

Faculty, Staff and Student Publications

No abstract provided.

A Tour Of Leukemia Progress In 2025, Viewed Through The Md Anderson Leukemia Research Lens, Hagop M Kantarjian, Gautam Borthakur, Naval Daver, Courtney Dinardo, Guillermo Garcia-Manero, Ghayas Issa, Elias Jabbour, Nitin Jain, Tapan Kadia, Sanam Loghavi, Farhad Ravandi, Guilin Tang, Mary Alma Welch, William Wierda

Faculty, Staff and Student Publications

Advances in the prognostication, monitoring, and treatment of both the acute and chronic leukemias have led to drastically improved outcomes over the past 2 decades. With the advent of targeted therapies, including antibodies such as blinatumomab and inotuzumab and small molecule inhibitors, such as the BCR::ABL1 tyrosine kinase inhibitors, Bruton tyrosine kinase inhibitors, and venetoclax, the treatment landscape of leukemia has drastically changed, improving survival outcomes while relying less on overall chemotherapy intensity in many leukemia types. This progress has allowed the categorization of more leukemia types as favorable (i.e., chronic lymphocytic leukemia, younger acute lymphoblastic leukemia [patients younger than …

Brain-Wide Patterns Of Crf Receptor 1 Expression In The Transgenic Crfr1-Cre-2a-Tdtom Rat, Douglas S Engelke, Lierni Ugartemendia, Jonathan Tao, Shivakumar Rajamanikam, Fabricio H Do Monte, Nicholas J Justice

Faculty, Staff and Student Publications

The ability to manipulate neurons that express corticotropin-releasing factor (CRF) or its receptors has led to many new discoveries about how CRF signaling modulates stress-related behaviors in mice. However, similar advances in rats have been limited by the lack of reporter lines targeting CRF receptors, restricting access to behavioral paradigms that are more suitable for, or specific to, rats. Here, we provide an extensive neuroanatomical characterization of a recently generated CRFR1-Cre rat. We show that Cre and tdTomato are expressed in a pattern that closely aligns with previously reported CRFR1 expression patterns, as determined by in situ hybridization in rats …

Probabilistic Template Matching For Detecting Resting-State Functional Mri Language Network In Brain Tumor Patients, Jian Ming Teo, Vinodh A Kumar, Alexander M Khalaf, Kyle R Noll, Sherise D Ferguson, Chibawanye I Ene, Sujit S Prabhu, Max Wintermark, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Intersubject variation among patients with brain tumors complicates the template matching process for detecting the resting-state (rs) functional MRI (fMRI) language network when using independent component analysis (ICA).

Purpose: This study aimed to develop methods that use a probabilistic language atlas to incorporate intersubject variation in brain tumor patients into the template matching process.

Methods: This retrospective study included 79 patients with brain tumors (average age, 50 ± 15 years) who underwent presurgical task-based (tb)-fMRI and rs-fMRI at clinical 3T scanners. At varying template generation thresholds (τ), binary and probabilistic templates were obtained from the language atlas. A binary …

Tagraxofusp, A Cd123-Targeted Therapy, For Chronic Myelomonocytic Leukemia: Final Results Of A Phase 1/2 Study, Mrinal M Patnaik, Haris Ali, Eunice S Wang, Abdulraheem Yacoub, James M Foran, Vikas Gupta, Gary J Schiller, Don Ambrose Stevens, Moshe Talpaz, Sarah Wall, Terra L Lasho, Abhishek A Mangaonkar, Talha Badar, Ross Lindsay, Antonio Galleu, Ira Gupta, Naveen Pemmaraju, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Chronic myelomonocytic leukemia (CMML) is an aggressive hematologic neoplasm characterized by an expansion of CD123+ monocytes and plasmacytoid dendritic cells (pDCs). pDC bone marrow clusters in CMML have been associated with higher rates of acute myeloid leukemia transformation. We evaluated tagraxofusp, a CD123-targeted therapy, in a phase 1/2 trial for patients with CMML. There were no dose-limiting toxicities. At the recommended phase 2 dose of 12 μg/kg per day, 37 patients were treated: 15 were treatment naïve; 22 had relapsed/refractory disease (median number of previous therapies, 1 [range, 1-7]). Common nonhematologic treatment-emergent adverse events (AEs) included fatigue (49%), hypoalbuminemia (46%), …

Sars-Cov-2 Mrna Vaccines Sensitize Tumours To Immune Checkpoint Blockade, Adam J Grippin, Christiano Marconi, Sage Copling, Nan Li, Chen Braun, Cole Woody, Elliana Young, Priti Gupta, Min Wang, Annette Wu, Seong Dong Jeong, Dhruvkumar Soni, Frances Weidert, Chao Xie, Eden Goldenberg, Andrew Kim, Chong Zhao, Anna Devries, Paul Castillo, Rishabh Lohray, Michael K Rooney, Benjamin R Schrank, Yifan Wang, Yifan Ma, Enoch Chang, Ramez Kouzy, Kyle Dyson, Jordan Jafarnia, Nina Nariman, Gregory Gladish, Jacob New, Ada Argueta, Diana Amaya, Nagheme Thomas, Andria Doty, Joe Chen, Nikhil Copling, Gabriel Alatrash, Julie Simon, Alicia Bea Davies, William Dennis, Richard Liang, Jeff Lewis, Xiong Wei, Waree Rinsurongkawong, Ara A Vaporciyan, Andrew Johns, D3code Team, Jack Lee, Ji-Hyun Lee, Ryan Sun, Padmanee Sharma, Hai Tran, Jianjun Zhang, Don L Gibbons, Jennifer Wargo, Betty Y S Kim, John V Heymach, Hector R Mendez-Gomez, Wen Jiang, Elias J Sayour, Steven H Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) extend survival in many patients with cancer but are ineffective in patients without pre-existing immunity1–9. Although personalized mRNA cancer vaccines sensitize tumours to ICIs by directing immune attacks against preselected antigens, personalized vaccines are limited by complex and time-intensive manufacturing processes10–14. Here we show that mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to ICIs. In preclinical models, SARS-CoV-2 mRNA vaccines led to a substantial increase in type I interferon, enabling innate immune cells to prime CD8+ T cells that target tumour-associated antigens. Concomitant ICI treatment is required for …

Surgical Outcomes With Neoadjuvant Durvalumab Plus Chemotherapy Followed By Adjuvant Durvalumab In Resectable Nsclc, Tetsuya Mitsudomi, John V Heymach, Martin Reck, Janis M Taube, Shugeng Gao, Yoshitsugu Horio, Jian You, Gaofeng Li, Dinh Van Luong, Somcharoen Saeteng, Fumihiro Tanaka, Stefan B Watzka, Laszlo Urban, Zsuzsanna Szalai, Hiroaki Akamatsu, Jin Hyoung Kang, Francisco J Orlandi, Guzel Z Mukhametshina, Andreas Pircher, Carlos Henrique Andrade Teixeira, Mike Aperghis, Gary J Doherty, Ruth Doake, Tamer M Fouad, David Harpole

Faculty, Staff and Student Publications

Introduction: In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival (p = 0.004) and pathologic complete response (p < 0.001; primary end points; modified intention-to-treat [mITT] population, which excluded patients with known EGFR or ALK aberrations) with a manageable safety profile in patients with resectable (R)-NSCLC. Here, we report surgical outcomes from AEGEAN.

Methods: Patients with treatment-naive R-NSCLC (stage II-IIIB [N2]) and Eastern Cooperative Oncology Group performance status 0 or 1 were randomized (1:1) to platinum-based chemotherapy plus durvalumab or placebo intravenously (every 3 wk, 4 cycles) before surgery, followed by durvalumab or placebo (every 4 wk, 12 cycles). Surgical outcomes were summarized for the mITT population using descriptive statistics.

Results: A total of 737 out of 740 mITT patients received treatment, 366 and 371 in the durvalumab and …

Study Of 18 F-Fluciclovine Pet For Serial Assessment Of Glioblastoma Tumor Volumes During Surgery And Radiotherapy, Samir A Dagher, Jason M Johnson, Rania M M Mohamed, Shehbaz Ansari, Osama Mawlawi, Ho-Ling Liu, Max Wintermark, Dawid Schellingerhout, Lesley Flynt, Debra N Yeboa, Jeffrey S Weinberg, Sherise D Ferguson, Maria K Gule-Monroe

Faculty, Staff and Student Publications

PURPOSE: Recent evidence supports incorporating 18 F-Fluciclovine PET for glioblastoma treatment planning and monitoring, as it better captures tumor infiltration compared to conventional MRI. However, the relationship between PET- and MRI-defined tumor volumes remains unclear, particularly in the post-treatment setting. This study prospectively compares tumor volumes on MRI and PET at multiple timepoints throughout the treatment course and evaluates volumetric changes with therapy.

METHODS: We prospectively enrolled 8 adults with IDH-wildtype glioblastoma treated with surgery and chemoradiation between September 2019 and 2021. Participants underwent paired 18 F-Fluciclovine PET/CT and conventional MRI at four timepoints: preoperatively, pre-radiation, and at one- and …

In Silico Assessment Of Cellular Damage From Lu-177, Ac-225, And Pb-212 Therapeutic Radionuclides, Konstantinos P Chatzipapas, Konstantinos Papachristou, Dimitris Visvikis, Sebastien Incerti, John D Hazle, George C Kagadis

Faculty, Staff and Student Publications

Background: Targeted radionuclide therapy (TRT) has emerged as a unique and effective treatment modality for cancer. Monte Carlo simulations have greatly advanced investigations into radiation-caused DNA damage, including the complexity of this damage.

Purpose: This study aimed to evaluate DNA damage induced by high-linear energy transfer therapeutic radionuclides used in TRT, specifically 225Ac, 177Lu, and 212Pb, using Geant4-DNA Monte Carlo simulations.

Methods: The Geant4-DNA toolkit, incorporating the "molecularDNA" example, was employed to simulate radiation interactions within a human fibroblast cell model featuring a fractal chromatin fiber geometry within an ellipsoidal nucleus. Three source geometries (membrane, cytoplasm, nucleus) were modeled to …

The Impact Of Social Determinants Of Health On Outcomes Of Brexucabtagene Autoleucel In Adults With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia, Timothy E O'Connor, Chenyu Lin, Gregory W Roloff, Amy Zhang, Katharine Miller, Ibrahim Aldoss, Noam E Kopmar, Simone E Dekker, Vishal K Gupta, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Naveed Ahmed, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Matthew P Connor, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Betsy Blunk, Aaron C Logan, Abdullah Ladha, Anjali S Advani, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Kristen M O'Dwyer, Laquisa C Hill, Joshua Sasine, Caspian Oliai, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu V Kumaran, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Vinod Pullarkat, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Bijal D Shah, Rawan Faramand, Lori S Muffly, Stephanie B Tsai, Bhagirathbhai Dholaria

Faculty, Staff and Students Publications

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023. Cox proportional hazards models evaluated the association of race, ethnicity, and SDoH with progression-free survival (PFS) and overall survival (OS). 189 patients received brexu-cel and 57% were male. 55% were non-Hispanic White, 30% Hispanic, 7% non-Hispanic Black, 6% Asian/Pacific …

Urinary Vitamin D Binding Protein And Kidney Injury Molecule-1 Are Potent Predictors Of Acute Kidney Injury After Left Ventricular Assist Device Implantation, Shiyi Li, Iván Murrieta-Álvarez, Katherine V Nordick, Zachary Gray, Camila Hochman-Mendez, Alexis E Shafii, Kenneth K Liao, Carl P Walther, Nandan K Mondal

Faculty, Staff and Students Publications

Background/Objectives: Acute kidney injury (AKI) is a frequent and serious complication following left ventricular assist device (LVAD) implantation. This study aimed to predict AKI within 90 days post-LVAD by evaluating urinary levels of vitamin D binding protein (VDBP) and kidney injury molecule-1 (KIM-1).

Methods: We prospectively enrolled 29 advanced heart failure patients undergoing LVAD implantation and categorized them into four groups based on pre-LVAD kidney function and hemodynamic stability. Early-morning urine samples were collected 24 h before and 1 week after surgery. Urinary VDBP and KIM-1 levels, normalized to creatinine, were measured.

Results: Thirteen patients developed AKI …

Resolving Slc6a1 Variable Expressivity With Deep Clinical Phenotyping And Drosophila Models, Kristy L Jay, Nikhita Gogate, Paige I Hall, Kimberly M Ezell, Jonathan C Andrews, Sharayu V Jangam, Hongling Pan, Kelvin Pham, Ryan German, Vanessa Gomez, Emily Jellinek-Russo, Eric A Storch, Brain Gene Registry Consortium, Undiagnosed Diseases Network, Shinya Yamamoto, Oguz Kanca, Hugo J Bellen, Herman A Dierick, Joy D Cogan, John A Phillips, Rizwan Hamid, Thomas Cassini, Lynette Rives, Sumit Pruthi, Hua-Chang Chen, Jennifer E Posey, Michael F Wangler

Faculty, Staff and Students Publications

Variants in SLC6A1 result in a rare neurodevelopmental disorder characterized by a variable clinical presentation of symptoms including developmental delay, epilepsy, motor dysfunction, and autism spectrum disorder. SLC6A1 haploinsufficiency has been confirmed as the predominant pathway of SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD); however, the molecular mechanism underlying the variable clinical presentation remains unclear. Here, through work of the Undiagnosed Diseases Network, we identify an individual with an inherited p.A334S variant of uncertain significance. To resolve this variant and better understand the variable expressivity associated with SLC6A1, we assess the phenotypes of the proband in comparison with a cohort of 13 individuals …

Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia Patients Have Dismal Outcomes Irrespective Of Allogeneic Hematopoietic Stem Cell Transplant: A Single-Center Experience, Gabriela Llaurador, Matthew Willis, Michele S Redell, M Monica Gramatges, Andrea N Marcogliese, Swati Naik, Robert Krance, Erin Doherty, Alexandra M Stevens

Faculty, Staff and Students Publications

Background: Pediatric non-Down Syndrome Acute Megakaryoblastic Leukemia (non-DS-AMKL) is a rare subtype of Acute Myeloid Leukemia (AML) arising from primitive megakaryocytes and is associated with poor outcomes. Given its high incidence of relapse, this subpopulation of children is frequently referred for allogeneic hematopoietic stem cell transplant (allo-HSCT) in first complete remission (CR1).

Objectives: The objective of this study was to describe the clinical outcomes of non-DS-AMKL pediatric patients in a large, single-institution cohort.

Methods: A retrospective review of the medical records of thirty-six patients diagnosed with non-DS-AMKL treated at Texas Children's Hospital from 2000 to 2022 was conducted.

Results: Twenty-nine …

Safety And Efficacy Of Liver-Directed Radiotherapy After Chemoimmunotherapy For Advanced Cholangiocarcinoma: An Early Report From A Large Tertiary Cancer Center, Abdulmoiz Asif, Abdulmoid Asif, Michael K Rooney, Enoch Chang, Felicity Namayanja, Kimana Quentin, Sunyoung Lee, Ian Hu, Vincent Bernard, Prajnan Das, Emma B Holiday, Sonal Noticewala, Grace L Smith, Albert C Koong, Ethan B Ludmir, Milind Javle, Lianchun Xiao, Eugene J Koay

Faculty, Staff and Student Publications

BACKGROUND: Recent randomized controlled trials have established chemoimmunotherapy as the standard of care for patients with advanced biliary cancers with a median overall survival (OS) of about thirteen months. No data exist to demonstrate the safety and efficacy of liver-directed radiotherapy (RT) for extrahepatic and intrahepatic cholangiocarcinoma (CCA) in the era of chemoimmunotherapy. The purpose of this study is to report our early experience treating patients with CCA using RT and chemoimmunotherapy.

METHODS: Twenty-eight patients with CCA who received chemoimmunotherapy sequentially and/or concurrently with RT were retrospectively analyzed. The median biologic equivalent dose (BED) of RT was 84.0 [interquartile range …

Runx2 Cooperates With Srebp1 To Rewire Cancer Metabolism And Promote Aggressiveness, Emanuele Vitale, Mila Gugnoni, Veronica Manicardi, Silvia Muccioli, Federica Torricelli, Benedetta Donati, Simonetta Piana, Gloria Manzotti, Elisa Salviato, Francesca Reggiani, Cristian Ascione, Rebecca Vezzani, Moira Ragazzi, Mattia Forcato, Oriana Romano, Silvio Bicciato, Aaron Goldman, Marco Tigano, Alessia Ciarrocchi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Embryonic Transcription Factors (TFs) are often reactivated in cancer, driving developmental gene programs that support phenotypic plasticity. Metabolic adaptation fuels this plasticity by supplying energy and molecular building blocks for growth. RUNX2, the master regulator of bone morphogenesis, is ectopically expressed in epithelial cancer, promoting metastasis through trans-differentiation processes like Epithelial-to-Mesenchymal Transition (EMT) and osteomimicry. By combining omics data with functional validation, we demonstrated that RUNX2 drives cancer cell metabolic rewiring by repressing mitochondrial respiration while promoting anabolic processes. We showed that RUNX2 upregulates key genes of lipid biosynthesis by regulating and cooperating with SREBP1. In vivo expression analysis in …

Understanding The Effects Of Real-Time Head Position Feedback On Postural Sway In Terms Of Changes In Underlying Deterministic And Stochastic Dynamical Processes, Steven J. Harrison, Benjamin De Bari, Ryan Poutre, Jeffrey M. Kinsella-Shaw

College of Humanities and Sciences Faculty Papers

Our perceptual systems detect information about how our body is moving relative to the surrounding environment. Such information is essential to our ability to maintain upright standing balance. Real-time postural feedback systems are technologies that appear to enhance our ability to detect information about the movements of our body, and as a consequence improve our capacity to control the posture of our body. Here we examine a system in which real-time measurements of head position were "felt" as changes in the intensity of vibration of tactors in a headband. Using this system, participants were able to stabilize their body posture, …

Distinct Molecular Responses Of Human Intestinal Organoids To Proton And Photon Radiation, Victoria Poplaski, Tajhal D Patel, Hoa Nguyen-Phuc, Amal Kambal, Lawrence Bronk, Mary K Estes, Cristian Coarfa, Sarah E Blutt

Faculty, Staff and Students Publications

Radiation exposure impairs rapidly renewing tissues like the intestinal epithelium, yet translational insights from murine models have been limited by species-specific responses. Here, we use human intestinal organoids (HIOs) derived from jejunal epithelium to evaluate human epithelial responses to low dose proton and photon (gamma) radiation. Gamma irradiation induces a unique developmental and metabolic shift in crypt-like organoids, including enrichment of amino acid metabolism pathways and activation of fetal-associated transcription factors and morphology. Integrated multi-omic profiling reveals serotonin biosynthesis as a central regenerative node. Human intestinal organoids can complement animal models and are emerging as a powerful tool in modeling …

Cohesin Haploinsufficiency Is Tolerated In Cbfb::Myh11-Driven Murine Acute Myeloid Leukemia, Shannon E Conneely, Alexis Quezada, Kristen J Kurtz, Nenggang Zhang, Josephine De La Fuente, Nesa Mercer, Jason H Rogers, Rogelio Aguilar, Geraldo Medrano, Margaret A Goodell, Paul P Liu, Debananda Pati, Rachel E Rau

Faculty, Staff and Students Publications

Cohesin gene mutations occur in many malignancies, including acute myeloid leukemia (AML). Loss-of-function mutations in the four major cohesin complex genes (RAD21, SMC3, SMC1a, and STAG2) occur across most major genetic subtypes of AML but are notably absent in AML harboring CBFB::MYH11, suggesting that cohesin mutations yield distinct biological outcomes dependent on the genetic AML driver. We hypothesized that CBFB::MYH11-expressing leukemias would be dependent on intact cohesin genes given their near-mutual exclusivity. To investigate this, we combined either germline or inducible heterozygous deletions in cohesin genes Smc3 or Rad21, respectively, with an inducible murine model of Cbfb::MYH11 AML. This approach …

A Single-Nucleus Transcriptomic Atlas Of The Adult Aedes Aegypti Mosquito, Olivia V Goldman, Alexandra E Defoe, Yanyan Qi, Yaoyu Jiao, Shih-Che Weng, Brittney Wick, Leah Houri-Zeevi, Priyanka Lakhiani, Takeshi Morita, Jacopo Razzauti, Adriana Rosas-Villegas, Yael N Tsitohay, Madison M Walker, Ben R Hopkins, Aedes Aegypti Mosquito Cell Atlas Consortium, Maximilian Haeussler, Omar S Akbari, Laura B Duvall, Helen White-Cooper, Trevor R Sorrells, Roshan Sharma, Hongjie Li, Leslie B Vosshall, Nadav Shai

Faculty, Staff and Students Publications

The female Aedes aegypti mosquito's remarkable ability to hunt humans and transmit pathogens relies on her unique biology. Here, we present the Aedes aegypti Mosquito Cell Atlas, a comprehensive single-nucleus RNA sequencing dataset of more than 367,000 nuclei from 19 dissected tissues of adult female and male Aedes aegypti, providing cellular-level resolution of mosquito biology. We identify novel cell types and expand our understanding of sensory neuron organization of chemoreceptors across all sensory tissues. Our analysis uncovers male-specific cells and sexually dimorphic gene expression in the antenna and brain. In female mosquitoes, we find that glial cells, rather than neurons, …

Longitudinal Characterization Of Males With X-Linked Creatine Transporter Deficiency: Final Results Of A Multiyear Observational Study, Judith S Miller, Cristan Farmer, Susan Blair, Simona Bianconi, Natacha Akshoomoff, Irina Anselm, Bruce A Barshop, Lindsey Becker, Amanda E Bennett, Leandra N Berry, Elizabeth M Berry-Kravis, Aleksandra Bruchey, Anna W Byars, Tricia Cimms, Kim M Cecil, Maxine Covello, Laura S Cubit, Tanvi Das, Robert J Davis, Madison Drye, Can Ficicioglu, John B Fulton, Robin P Goin-Kochel, Whitney Guthrie, Barbara E Hallinan, Fady Hannah-Shmouni, Kathryn E Gustafson, Dwight D Koeberl, Nicola Longo, Eva Mamak, Saadet Mercimek-Andrews, Claire Michalak, Forbes D Porter, Samar Rahhal, Linda Rees, Gail A Spiridigliozzi, Caitlin Stone, Nancy R Sullivan, V Reid Sutton, Rebecca P Thomas, Manisha Udhnani, Susan Waisbren, Michelle Xu, Lin Zhang, Melanie Brandabur, Audrey Thurm

Faculty, Staff and Students Publications

Background: The purpose of the Vigilan observational study (ClinicalTrials.gov, NCT02931682) was to prospectively assess the natural history and developmental course of creatine transporter deficiency (CTD).

Methods: Males with CTD aged 6 months to 65 years were evaluated at 6-month intervals for up to 4 years. Evaluations included neurodevelopmental assessments of intellectual functioning, adaptive functioning, and challenging behaviors and the onset and progression of medical comorbidities.

Results: Fifty participants (median age, 7.6 years) were enrolled. The predominant CTD phenotype consisted of significant intellectual disabilities and limited skill development over time. Most participants had a history of febrile or nonfebrile seizures, …