WIP - Monarch Accelerator Program to Engineering: A Reflection on the First Semester

2025-08-21

This work in progress paper examines the Monarch Accelerator Program to Engineering (MAP2E) program. The MAP2E Program was developed to assist students who desire to become engineers but may need additional assistance in math and science. and it allows students to develop their math and science skills while creating a pathway to personal or professional enriching skills. Furthermore, the MAP2E program allows students to develop their math and science skills and create parallel pathways to personal or professionally enriching skills. For instance, a student may hope to one day start their own engineering firm. A business administration pathway would allow students to become engineers while learning accounting, economics, and financial planning skills, enhancing their career prospects. As part of the MAP2E program, students participated in a one-week summer transition program to help students build their engineering identity and develop core competencies [1-3]. During the academic year, students became part of an Impact Learning Community (ILC), where they took engineering, math, and science courses together. The ILC also includes weekly meetings, group meetings, intrusive advising practices, field trips, guest speakers, and a study center with tutoring and supplemental instruction. This work in progress paper will present reflections from our first semester.

Non-Invasive Pancreas Ablation Using Histotripsy: Pre-clinical Safety Study in an In Vivo Porcine Model

Ultrasound in Medicine & Biology · 2025-10-03 · 2 citations

Abstract 1456: First successful engraftment of human liver cancer cell line in highly robust immunocompromised porcine model to test the tumor ablation efficacy by histotripsy

Cancer Research · 2024-03-22 · 1 citations

Abstract Liver tumor, commonly called Hepatocellular carcinoma(HCC), is the most common type of primary liver malignancy. It is the fourth leading cause of cancer-related deaths. Late diagnosis, location of the tumor, tumor burden, and metastases makes liver tumor very challenging to treat by liver transplantation, surgical procedures, and other ablation techniques like cryoablation and thermal ablation. Also, the absence of a preclinical animal model makes it challenging to develop and explore the feasibility of treatment modalities. Histotripsy is a non-invasive, non-ionizing, non-thermal, image-guided focused ultrasound ablation treatment method that uses high-pressure pulses to create acoustic cavitation, a “bubble cloud,” at the target. The bubble cloud expands and collapses, which ablates the tissue into an acellular homogenate. Pigs are ideal animal models as they closely resemble human anatomy and are significant in improving the translation to human patients. This study aimed to establish the feasibility of successfully ablating liver tumors by histotripsy using an immunocompromised porcine model to generate HepG2 human liver cancer cell line tumors in the liver of the immunocompromised pigs. The orthotopic porcine model was established using RAG2/IL2RG double knockout immunocompromised pigs. HepG2 cells were injected orthotopically into the liver of immunocompromised pigs. Three weeks after the injections, CT images and necropsy indicated successful engraftment and growth of liver tumors in the pigs. The ultrasound images and post-histotripsy treatment histology images showed confirmed ablation zones in the liver. Therefore, in conclusion, our preliminary results in the study could demonstrate, for the first time, a highly robust model of human liver cancer in a large animal model. Soon, we plan to conduct more such studies and explore all the possible utilities of these immunocompromised porcine models to develop therapeutic strategies to increase the efficacy of liver tumor ablation by histotripsy. Citation Format: Tamalika Paul, Khan M. Imran, Jessica Gannon, Brie Trusiano, Kristin Eden, Hannah Ivester, Madeline Mott, Manali Powar, Michael Edwards, Christopher Byron, Sherrie Clark-Deener, Kiho Lee, Eli Vlaisavljevich, Irving Coy Allen. First successful engraftment of human liver cancer cell line in highly robust immunocompromised porcine model to test the tumor ablation efficacy by histotripsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1456.

NF-κB Inducing Kinase Attenuates Colorectal Cancer by Regulating Noncanonical NF-κB Mediated Colonic Epithelial Cell Regeneration

Cellular and Molecular Gastroenterology and Hepatology · 2024-01-01 · 11 citations

BACKGROUND & AIMS: Dysregulated colonic epithelial cell (CEC) proliferation is a critical feature in the development of colorectal cancer. We show that NF-κB-inducing kinase (NIK) attenuates colorectal cancer through coordinating CEC regeneration/differentiation via noncanonical NF-κB signaling that is unique from canonical NF-kB signaling. METHODS: ) and conditional-knockout mice following administration of azoxymethane and dextran sulfate sodium. RESULTS: ). CONCLUSIONS: Dysregulated noncanonical NF-κB signaling is associated with the development of colorectal cancer in a tissue-dependent manner and defines a critical role for NIK in regulating gastrointestinal inflammation and regeneration associated with colorectal cancer.

Ultrasound-guided noninvasive pancreas ablation using histotripsy: feasibility study in an <i>in vivo</i> porcine model

International Journal of Hyperthermia · 2023-08-29 · 16 citations

Pancreatic cancer is a malignant disease associated with poor survival and nearly 80% present with unresectable tumors. Treatments such as chemotherapy and radiation therapy have shown overall improved survival benefits, albeit limited. Histotripsy is a noninvasive, non-ionizing, and non-thermal focused ultrasound ablation modality that has shown efficacy in treating hepatic tumors and other malignancies. In this novel study, we investigate histotripsy for noninvasive pancreas ablation in a pig model. In two studies, histotripsy was applied to the healthy pancreas in 11 pigs using a custom 32-element, 500 kHz histotripsy transducer attached to a clinical histotripsy system, with treatments guided by real-time ultrasound imaging. A pilot study was conducted in 3 fasted pigs with histotripsy applied at a pulse repetition frequency (PRF) of 500 Hz. Results showed no pancreas visualization on coaxial ultrasound imaging due to overlying intestinal gas, resulting in off-target injury and no pancreas damage. To minimize gas, a second group of pigs (n = 8) were fed a custard diet containing simethicone and bisacodyl. Pigs were euthanized immediately (n = 4) or survived for 1 week (n = 4) post-treatment. Damage to the pancreas and surrounding tissue was characterized using gross morphology, histological analysis, and CT imaging. Results showed histotripsy bubble clouds were generated inside pancreases that were visually maintained on coaxial ultrasound (n = 4), with 2 pigs exhibiting off-target damage. For chronic animals, results showed the treatments were well-tolerated with no complication signs or changes in blood markers. This study provides initial evidence suggesting histotripsy’s potential for noninvasive pancreas ablation and warrants further evaluation in more comprehensive studies.

Successful In Situ Targeting of Pancreatic Tumors in a Novel Orthotopic Porcine Model Using Histotripsy

Ultrasound in Medicine & Biology · 2023-08-16 · 7 citations

ObjectiveNew therapeutic strategies and paradigms are direly needed to treat pancreatic cancer. The absence of a suitable pre-clinical animal model of pancreatic cancer is a major limitation to biomedical device and therapeutic development. Traditionally, pigs have proven to be ideal models, especially in the context of designing human-sized instruments, perfecting surgical techniques and optimizing clinical procedures for use in humans. However, pig studies have typically focused on healthy tissue assessments and are limited to general safety evaluations because of the inability to effectively model human tumors.MethodsHere, we establish an orthotopic porcine model of human pancreatic cancer using RAG2/IL2RG double-knockout immunocompromised pigs and treat the tumors ex vivo and in vivo with histotripsy.ResultsUsing these animals, we describe the successful engraftment of Panc-1 human pancreatic cancer cell line tumors and characterize their development. To illustrate the utility of these animals for therapeutic development, we determine for the first time, the successful targeting of in situ pancreatic tumors using histotripsy. Treatment with histotripsy resulted in partial ablation in vivo and reduction in collagen content in both in vivo tumor in pig pancreas and ex vivo patient tumor.ConclusionThis study presents a first step toward establishing histotripsy as a non-invasive treatment method for pancreatic cancer and exposes some of the challenges of ultrasound guidance for histotripsy ablation in the pancreas. Simultaneously, we introduce a highly robust model of pancreatic cancer in a large mammal model that could be used to evaluate a variety biomedical devices and therapeutic strategies. New therapeutic strategies and paradigms are direly needed to treat pancreatic cancer. The absence of a suitable pre-clinical animal model of pancreatic cancer is a major limitation to biomedical device and therapeutic development. Traditionally, pigs have proven to be ideal models, especially in the context of designing human-sized instruments, perfecting surgical techniques and optimizing clinical procedures for use in humans. However, pig studies have typically focused on healthy tissue assessments and are limited to general safety evaluations because of the inability to effectively model human tumors. Here, we establish an orthotopic porcine model of human pancreatic cancer using RAG2/IL2RG double-knockout immunocompromised pigs and treat the tumors ex vivo and in vivo with histotripsy. Using these animals, we describe the successful engraftment of Panc-1 human pancreatic cancer cell line tumors and characterize their development. To illustrate the utility of these animals for therapeutic development, we determine for the first time, the successful targeting of in situ pancreatic tumors using histotripsy. Treatment with histotripsy resulted in partial ablation in vivo and reduction in collagen content in both in vivo tumor in pig pancreas and ex vivo patient tumor. This study presents a first step toward establishing histotripsy as a non-invasive treatment method for pancreatic cancer and exposes some of the challenges of ultrasound guidance for histotripsy ablation in the pancreas. Simultaneously, we introduce a highly robust model of pancreatic cancer in a large mammal model that could be used to evaluate a variety biomedical devices and therapeutic strategies.

Ultrasound-guided noninvasive pancreas ablation using histotripsy: feasibility study in an <i>in vivo</i> porcine model

Figshare · 2023-01-01

Pancreatic cancer is a malignant disease associated with poor survival and nearly 80% present with unresectable tumors. Treatments such as chemotherapy and radiation therapy have shown overall improved survival benefits, albeit limited. Histotripsy is a noninvasive, non-ionizing, and non-thermal focused ultrasound ablation modality that has shown efficacy in treating hepatic tumors and other malignancies. In this novel study, we investigate histotripsy for noninvasive pancreas ablation in a pig model. In two studies, histotripsy was applied to the healthy pancreas in 11 pigs using a custom 32-element, 500 kHz histotripsy transducer attached to a clinical histotripsy system, with treatments guided by real-time ultrasound imaging. A pilot study was conducted in 3 fasted pigs with histotripsy applied at a pulse repetition frequency (PRF) of 500 Hz. Results showed no pancreas visualization on coaxial ultrasound imaging due to overlying intestinal gas, resulting in off-target injury and no pancreas damage. To minimize gas, a second group of pigs (<i>n</i> = 8) were fed a custard diet containing simethicone and bisacodyl. Pigs were euthanized immediately (<i>n</i> = 4) or survived for 1 week (<i>n</i> = 4) post-treatment. Damage to the pancreas and surrounding tissue was characterized using gross morphology, histological analysis, and CT imaging. Results showed histotripsy bubble clouds were generated inside pancreases that were visually maintained on coaxial ultrasound (<i>n</i> = 4), with 2 pigs exhibiting off-target damage. For chronic animals, results showed the treatments were well-tolerated with no complication signs or changes in blood markers. This study provides initial evidence suggesting histotripsy’s potential for noninvasive pancreas ablation and warrants further evaluation in more comprehensive studies.

Horseshoe kidney: Morphologic features, embryologic and genetic etiologies, and surgical implications

Clinical Anatomy · 2023 · 16 citations

• Medicine
• Pathology
• Surgery

The horseshoe kidney (HSK) is the most common congenital abnormality of the upper urinary tract with an incidence of approximately 1 in 500 in the general population. Although individuals with HSK are often asymptomatic, they are at increased risk for neoplasms, infections, ureteropelvic obstruction secondary to lithiasis or vascular compression. Direct injury from trauma is increased in these individuals as is the risk of intraoperative complications secondary to damage involving the typically complex renal or adrenal vascular supply. We briefly review etiological factors including renal and urinary system embryology, genetic mutations, abnormalities related to faulty cell signaling, aberrant cell migration, and other possible causes including environmental exposures and trauma. In addition, we call attention to factors that might influence the success of surgical procedures in patients with HSK. We argue that an understanding of possible etiologies of the HSK and its different subtypes may be useful when planning surgical procedures or considering risk-benefit ratios associated with different surgical options. We briefly present the organization of a HSK in a 100-year-old male demonstrating an unusual vascular supply discovered during a dissection laboratory session in a medical school anatomy course. We describe the structure of the HSK, the position and relationships of the HSK to other structures within the abdomen, and the associated vascular relationships.

An integrated pre-clerkship curriculum to build cognitive medical schema: It’s not just about the content

Frontiers in Physiology · 2023 · 4 citations

• Computer Science
• Computer Science
• Psychology

Both physiology and pathophysiology are essential disciplines in health professional education however, clinicians do not use this knowledge in isolation. Instead, physicians use inter-disciplinary concepts embedded within integrated cognitive schema (illness scripts) established through experience/knowledge that manifest as expert-level thinking. Our goal was to develop a pre-clerkship curriculum devoid of disciplinary boundaries (akin to the physician's illness script) and enhance learners' clerkship and early clinical performance. As well as developing curricular content, the model considered non-content design elements such as learner characteristics and values, faculty and resources and the impact of curricular and pedagogical changes. The goals of the trans-disciplinary integration were to develop deep learning behaviors through, 1) developing of integrated, cognitive schema to support the transition to expert-level thinking, 2) authentic, contextualization to promote knowledge transfer to the clinical realm 3) allowing autonomous, independent learning, and 4) harnessing the benefits of social learning. The final curricular model was a case-based approach with independent learning of basic concepts, differential diagnosis and illness scripting writing, and concept mapping. Small-group classroom sessions were team-taught with basic scientists and physicians facilitating learners' self-reflection and development of clinical reasoning. Specifications grading was used to assess the products (written illness scripts and concept maps) as well as process (group dynamics) while allowing a greater degree of learner autonomy. Although the model we adopted could be transferred to other program settings, we suggest it is critical to consider both content and non-content elements that are specific to the environment and learner.

EGR2 deletion displays similar and differential effects on immunological development and function in autoinflammation-prone B6/lpr and normal B6 mice

The Journal of Immunology · 2022-05-01

Abstract Transcription factor early growth response protein 2 (EGR2) prevents the development of lupus-like autoimmune disease in C57BL/6 (B6) mice by negatively regulating T cell activation, inflammatory cytokine IFNγ and IL-17 production and by suppressing humoral responses. However, increased EGR2 expression has been observed in lupus and also other autoimmune disorders, which contradicts the autoimmune suppressive role of EGR2. Here, we derived conditional EGR2−/− B6/lpr and EGR2−/− B6 mice to investigate and compare the immune regulatory role of EGR2 in autoinflammation (B6/lpr) versus normal physiological (B6) conditions. Significantly, we found that in B6/lpr mice, but not in B6 mice, EGR2 deletion dramatically suppressed serum levels of anti-dsDNA autoantibodies, total IgG, IgG1, IgG2a, and IgM. We further demonstrated that while EGR2 deletion promoted germinal center B (GCB) cell development in both B6 and B6/lpr mice, it significantly reduced the differentiation of plasma and plasmablasts cells in B6/lpr mice. EGR2 deletion promoted splenomegaly and T cell activation in both B6 and B6/lpr mice, but it differentially regulated the profiles of immune cell subpopulations in the spleens of B6 and B6/lpr mice. Especially, EGR2 deletion dramatically suppressed the development of double negative T cells in B6/lpr mice. Moreover, we found that EGR2 had an opposite role in regulating IL-17 production in in vitro activated splenocytes from B6/lpr and B6 mice, although EGR2 had a similar suppressive role for IFNγ production. Together, our data strongly suggest that the immune and autoimmune regulatory roles of EGR2 are context dependent, and should not be generalized in normal physiology and different pathological conditions. Supported by VMCVM-VCOM Center for One Heath Research Seed Grant Program