Cell and Developmental Biology Commons^™

Chimeric Antigen Receptor Structure And Manufacturing Of Clinical Grade Car Engineered Cells Using Different Bioreactors, Farhatullah Syed, Riad El Fakih, Ali Debsan Alahmari, Ahmed Syed Osman Ali, Mahmoud Aljurf

Hematology/Oncology and Stem Cell Therapy

Increasing success of adaptive cell therapy (ACT), such as genetically engineered T cells to express chimeric antigen receptors (CARs) proven to be highly significant technological advancements and impressive clinical outcomes in selected haematological malignancies, with promising efficacy. The evolution of CAR designs beyond the conventional structures is necessary to address some of the limitations of conventional CAR therapy and to expand the use of CAR T cells to a wider range of malignancies. There are various obstacles with a wide range of engineering strategies in order to improve the safety, efficacy and applicability of this therapeutic modality. Here we describe …

Lisocabtagene Maraleucel In Relapsed Or Refractory Diffuse Large B Cell Lymphoma: What Is The Evidence?, Mohamed A. Kharfan-Dabaja, Farah Yassine, Muhamad Alhaj Moustafa, Madiha Iqbal, Hemant Murthy

Hematology/Oncology and Stem Cell Therapy

Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T cell product, with a CD3f activatory domain connected to 4-1BB costimulatory domain. Liso-cel, unlike the other two approved products—axicabtagene ciloleucel and tisagenlecleucel— is manufactured separately from CD4 and CD8 T cells and then administered as a sequential infusion of the two components at equal target doses. The approval of liso-cel was based on the results of Transcend NHL 001, a single-arm, open-label, multicenter, seamless design trial that enrolled 344 patients, of whom 269 received conforming liso-cel. The most common histology was diffuse large B cell lymphoma, not otherwise …

Cytogenetic Influence On Prognosis In Acute Promyelocytic Leukaemia: A Cohort Study In Vietnam, Minh Phuong Vu, Cuc Nhung Nguyen, Hoang Vu

Hematology/Oncology and Stem Cell Therapy

Objective/Background: To analyse the influence of chromosomal aberrations in addition to t (15;17)(q22;q21) in acute promyelocytic leukaemia (APL) on clinical characteristics and treatment outcomes. Methods: Fifty-seven patients with new APL diagnoses underwent conventional cytogenetic analysis; fluorescence in situ hybridization for t(15;17)(q22;q21) and reverse transcriptase–p olymerase chain reaction detected PML/RARa in two forms: L (length) and S (short) and accepted treatment with all-trans retinoic acid and chemotherapy. Patients with additional chromosome aberrations were designated as the complex karyotype group and were compared with patients with only t(15;17), who were designated as the simple karyotype group. Results: Additional chromosome aberrations was observed …

Priapism In Lymphoproliferative Disorders: A Systematic Review, Elrazi A. Ali, Sundus Sardar, Mohamed A. Yassin

Hematology/Oncology and Stem Cell Therapy

Priapism is defined as a persistent penile erection lasting more than 4 h. We searched the literature for reviews, case reports, and series for patients with lymphoproliferative disorders who developed priapism. The search involved all the lymphoproliferative disorders included in the revised 2016 World Health Organization classification of lymphoid neoplasms including chronic lymphocytic leukemia, multiple myeloma, Waldenstro¨m macroglobulinemia, and lymphomas. A total of 16 articles were found. The search included cases up to 4th January 2021. Priapism was seen most commonly as the first manifestation of lymphoproliferative disorders, rarely seen after treatment or after diagnosis.

Prevalence Of Sleep Aid Medication Use In Patients Receiving A Hematopoietic Cell Transplant On An Inpatient Unit, Rachel Cusatis, Antony Ibrahim, Jennifer M. Knight, Anita D'Souza, Bronwen E. Shaw

Hematology/Oncology and Stem Cell Therapy

Background and objectives: There is a lack of research regarding the use of sleep aids after hematopoietic stem cell transplantation (HCT). We describe the prevalence of sleep aid administration in the HCT unit and identify associations with patient or clinical characteristics. Patients and methods: In this retrospective analysis of sequential inpatient HCTs from July 1 to December 31, 2016 we describe whether and when patients were prescribed sleep aid medications. Chi-square tests determined significant differences between patient characteristics, sleep aid prescription, and time of prescription. Results: Of the 225 patients identified, 193 (86%) were prescribed sleep aids. Significantly more women …

Hematologic Manifestations Of Parvovirus B 19 Infection, Ghada Algwaiz, Abrar Alharbi, Khuloud Alsehaim, Ali Alahmari, Riad El Fakih, Mahmoud Aljurf

Hematology/Oncology and Stem Cell Therapy

Parvovirus B19 virus infection is widespread among humans because of its highly infectious and obstinate nature, with up to 80% of the population testing positive for IgG antibodies against the virus. Pronormoblasts observed in biopsy are the hallmarks of PVB19 infection. In addition, PVB19 affects the skin, heart, brain, joints, and liver and can be diagnosed through antibody detection or DNA detection via PCR. Due to its capsid proteins’ high affinity for bone marrow receptors, its main presentation is the suppression of bone marrow functions. It has been shown to affect patients with hemolytic anemia and patients with hematological malignancies, …

Modulation Of Polyamines To Elucidate Function Within Osteogenesis Of Mesenchymal Stromal Cells, Amin S. Cressman

Cal Poly Humboldt theses and projects

Snyder-Robinson Syndrome (SRS), an X-linked intellectual disability that arises in children, exhibits debilitating phenotypes like severe osteoporosis. These patients demonstrate an inability to produce mineralized new bone in comparison to the rate at which bone is resorbed, thus leading to weaker skeletal structure and atraumatic fractures. The known cause of SRS is due to loss-of-function mutations within the gene that encodes Spermine Synthase (SMS). Loss of SMS enzymatic activity, which catalyzes the conversion of polyamines spermidine into spermine, demonstrates an increase in the spermidine/spermine ratio in all documented cases of this disorder. The involvement of polyamines in osteogenesis is still …

Determining Haplotype Specific X Chromosome Inactivation State And Related Epigenetic Features In Female X-Linked Genes, Ariah Dawn Mackie

Cal Poly Humboldt theses and projects

Females with heterozygous X-linked mutations are prone to pseudo-haploinsufficiency because random X chromosome inactivation (XCI) silences one of their two X chromosomes. A prior study explored the theory that reactivating the silenced healthy allele could be a treatment for pseudo-haploinsufficient females. The next step was to evaluate this approach in a clinically relevant stem cell model of the rare neurological disease CDKL5 Deficiency Disorder (CDD). It was necessary to validate X-inactivation state with respect to CDKL5 allele expression in one of these models. We explored CDKL5 allele expression in two populations of CDD female patient-derived induced pluripotent stem cells (iPSCs) …

Evaluating Novel Combinations Of Polyamine Targeting Therapeutics In Pancreatic Ductal Adenocarcinoma, Sai Preethi Nakkina

Electronic Theses and Dissertations, 2020-

Pancreatic cancer overall has a poor five-year survival rate of less than 8%. Well-tolerated regimens and immune cell infiltration to promote anti-cancer treatments are major challenges. Studies described herein leveraged testing different combinations/doses of polyamine targeting inhibitors to further understand the impact of targeting key polyamine pathway mediators in pancreatic ductal adenocarcinoma (PDAC). Placebo controls were compared to groups treated with difluoromethylornithine (DFMO, a polyamine biosynthesis inhibitor of ornithine decarboxylase), different polyamine transport inhibitors, and compound combinations in strategies for polyamine blockage therapy (PBT). Informatic analyses showed that the dysregulation of key polyamine pathway mediators are associated with poor patient …

Alternative Splicing Regulates The Innate Immune Response To Viral Infection, Luke A. White

Graduate Student Theses, Dissertations, & Professional Papers

Rift Valley fever virus (RVFV) is a mosquito-borne RNA virus that infects humans and livestock in sub-Saharan Africa and the Arabian peninsula, causing disease ranging from a mild flu-like illness to liver damage, blindness, hemorrhagic fever, death, and, especially in livestock animals, high rates of abortive pregnancies. There is no approved vaccine for RVFV, and as a disease with a high rate of spread that causes severe illness, it is listed as a Category A pathogen by the USA CDC. A better understanding of RVFV’s molecular virology will be instrumental to combating RVFV as climate change causes its mosquito host …

Elucidating The Role Of Hemodynamic Force In Regulating The Attachment Of Vascular Smooth Muscle Cells (Vsmcs) To Maturing Vessels During Mouse Embryonic Development, Israt Jahan

MSU Graduate Theses

Blood vessel maturation is characterized by the recruitment and attachment of vascular smooth muscle cells (vSMCs) around immature blood vessels, which ultimately form the tunica media. Improper maturation can lead to vascular birth defects ranging from minor birthmarks to lethal brain aneurysms. Previously, our lab demonstrated that hemodynamic force plays an important role to regulate vSMCs recruitment from neighboring low-flow to high-flow vessels followed by the attachment of these vSMCs to the high-flow vessels. To understand the reason for the preferred attachment of vSMCs to high-flow vessels, instead of low-flow vessels, I hypothesize that hemodynamic force modulates the expression of …

Elucidating The Role Of Kmt2d In Her2+ Breast Cancer, Emily Ma

Dissertations

Breast cancer is the second leading cause of cancer-related deaths among women in the US. Histone modifications are common epigenetic changes that have been implicated in several breast cancers, including HER2+ breast cancers. Current therapies, such as trastuzumab, block the HER2 receptor to reduce tumor growth. Unfortunately, HER2+ breast cancers have found ways to overcome these therapies, leading to tumor resistance, metastases, and poor survival outcomes. A better understanding of the underlying mechanisms contributing to HER2+ breast cancer resistance may lead to the discovery of novel therapeutic strategies to improve patient outcomes.One prognostic marker for poor survival in women with …

Genetic Underpinnings Of Novel Trait Development In A Euwallacea-Fusarium Mutualism, Elaina J. Spahr

Graduate Theses, Dissertations, and Problem Reports

Evolutionary Developmental Biology seeks to answer fundamental questions about the mechanisms underlying the evolution and innovation towards increasing structural complexity within the body plan. The ambrosia symbiosis, a polyphyletic group of xylem-feeding beetles, provides a wealth of diversity in novel pouch-like structures called mycangia. This diversity could serve as a rich model for understanding how mutualisms may prompt structural innovation and diversification in a host organism. The ambrosia symbiosis has become a fast-growing research subject in entomology and forest pathology but has yet to experience the same attention under the lens of evolutionary developmental genetics.

Development of mycangia was examined …

Characterization Of Two Krab-Containing Zinc Finger Transcription Factors In Bovine Preimplantation Embryonic Development, Mingxiang Zhang

Graduate Theses, Dissertations, and Problem Reports

Oocyte developmental competence or oocyte intrinsic quality describes the capability of oocytes to resume meiosis, cleave and develop to blastocyst stage after fertilization, implant and develop to term in a good health. A growing number of evidences indicate that the majority of embryonic mortality occurs during early embryonic development in different species, including human, horse and cattle primarily due to poor oocyte quality. Maternal effect genes are key aspects of oocyte quality, which are transcribed during the process of oogenesis and folliculogenesis. The maternal factors are accumulated in oocytes, orchestrating various early developmental events including fertilization, epigenetic reprogramming and zygotic …

Identifying Adp-Ribosylation As The Biochemical Signal That Marks Dna-Protein Crosslinks For Sprtn-Dependent Proteolysis, Katelyn Hurley

Electronic Theses and Dissertations

DNA-protein crosslinks (DPCs) form when proteins covalently attach to DNA. It is estimated that hundreds of DPCs form in our cells each day. Because these lesions are cytotoxic, mammalian cells have evolved multiple intricate repair systems to remove DPCs and restore genome integrity. One mechanism mammalian cells rely on for DPC repair is direct proteolysis by the metalloprotease, SPRTN. While it is known that SPRTN degrades a heterogenous array of DPCs, including both naturally occurring and chemically induced, how SPRTN selects DPCs amongst chromatin-associated proteins remains unknown. Our main objective is to determine how DPC repair is regulated. In Chapter …

Characterizing The Lir Domain Of Abin1 And Identifying Its Role As A Regulator Of Mitophagy, Andrew Rhiner

Electronic Theses and Dissertations

A20 Inhibitor of NF-κB (ABIN1/TNIP1) is a known regulator of TNFα signaling induced cell death and inflammation. The regulatory activity has been attributed to ABIN1’s recruitment of the ubiquitin editing enzyme TNF-α-induced protein 3 (TNFAIP3/A20) to Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). The regulation of RIPK1 by ABIN1 and A20 relies on a third player, linear ubiquitin chain assembly complex (LUBAC), which is involved in the recruitment of ABIN1 to RIPK1. Loss of LUBAC or ABIN1 is embryonic lethal, but loss of A20 is not embryonic lethal. The embryonic lethality due to loss of ABIN1, paired with the lack of lethality …

Phip Variants Associated With Chung–Jansen Syndrome Disrupt Replication Fork Stability And Genome Integrity, Neysha Tirado-Class, Caitlin Hathaway, Wendy K. Chung, Huzefa Dungrawala

Molecular Biosciences Faculty Publications

Chung–Jansen syndrome (CJS) is a rare, autosomal dominant disorder characterized by developmental delay, intellectual disability/cognitive impairment, behavioral challenges, obesity, and dysmorphic features. CJS is associated with heterozygous variants in PHIP (Pleckstrin-Homology Interacting Protein), a gene that encodes one of several substrate receptors for Cullin4-RING (CRL4) E3 ubiquitin ligase complex. Full-length PHIP, also called DCAF14, was recently identified to function as a replication stress response protein. Herein, we report the identification of two PHIP missense variants identified by exome sequencing in unrelated individuals with CJS. The variants p.D488V and p.E963G occur in different functional elements of DCAF14-WD40 repeat domain and pleckstrin …

Sequence Properties Of An Intramolecular Interaction That Inhibits P53 Dna Binding, Emily Gregory, Gary W. Daughdrill

Molecular Biosciences Faculty Publications

An intramolecular interaction between the p53 transactivation and DNA binding domains inhibits DNA binding. To study this autoinhibition, we used a fragment of p53, referred to as ND WT, containing the N-terminal transactivation domains (TAD1 and TAD2), a proline rich region (PRR), and the DNA binding domain (DBD). We mutated acidic, nonpolar, and aromatic amino acids in TAD2 to disrupt the interaction with DBD and measured the effects on DNA binding affinity at different ionic strengths using fluorescence anisotropy. We observed a large increase in DNA binding affinity for the mutants consistent with reduced autoinhibition. The ΔΔG between DBD and …

Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson

Graduate Theses, Dissertations, and Problem Reports

Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …

The Effects Of Neuronal Growth Factors On Lps-Activated Schwann Cells, Caitlyn E. Henry, Peyton Kimmel, Angela Asirvatham Ph.D.

Student Research Poster Presentations 2022

Schwann cells (SCs) are the principal support cells of neurons in the peripheral nervous system, that both myelinate axons for the rapid conduction of electrical impulses as well as assist in axonal repair during nerve injury. During nerve injury, SCs secrete tumor necrosis factor alpha (TNF-α)^1,5,6 and other proinflammatory mediators^1,6, attracting macrophages to the site of injury to induce inflammation and clear myelin debris.^1,6 Once the debris is cleared, the neuron stimulates SC proliferation by secreting neuronal mitogens, such as heregulin^3,4, and an unknown factor that activates the cAMP pathway³, an important …