Shoeb Lallani

All Publications

• Modulation of the p75 neurotrophin receptor in the PS19 tauopathy mouse model regulates transcription profiles and inter-cellular communication across multiple populations of non-neuronal cells Butler, R. R., Yang, T., Han, C., Le Guen, Y., Tran, K. C., Lallani, S., Liu, H., Leng, S., Massa, S. M., Longo, F. M. WILEY. 2023

  View details for DOI 10.1002/alz.080789

  View details for Web of Science ID 001197662100003

• A course in medical device design & commercialization for medical students pursuing surgical fields. American journal of surgery DeLay, T. K., Harris, J. B., Willis, J. G., Lallani, S., Obinwa, C., Berg, I. C., Eberhardt, A. W. 2023; 225 (4): 667-672

  Abstract

  The modern surgeon faces an ever-changing landscape of procedural innovation. The demands of present-day healthcare highlight the importance of successfully developing new medical devices and technologies. This effort requires multidisciplinary collaborations of professionals ranging from manufacturers and engineers to researchers and healthcare providers. Surgeons regularly interact with complex equipment and user interfaces without substantial formal education on their design and development. The objective of this study was to ascertain the impact of a 10-week BME course into a medical school curriculum on surgery-bound students' knowledge of product design and gauge their ability to develop an actual product to meet a real need in a surgical field.A Medical Device Design and Commercialization co-enrolled elective course was offered to medical students at a single institution. Five students with an expressed surgical and procedural interest were enrolled. At the beginning of the course, they were tasked with developing a product to meet a clinical need they observed. At the conclusion of the course, students filled out a questionnaire about their level of comfort and knowledge of the material using a 5-point Likert scale. This survey was administered to a control group of medical students who did not take the course.The BME student cohort was able to successfully identify a post-operative need, develop a prototype of a novel device, and present their product to attending surgeons. A total of 35 survey entries were received: five from the experimental group and 30 from the comparison group. The experimental group scored higher than the comparison group for all survey questions and reached the level of statistical significance in 13 of the 15 questions (p < 0.05). Survey respondents reported similar degrees of knowledge and comfort in recognizing unmet needs in a hospital setting and formulating a comprehensive statement describing them.The principles of biomedical engineering are integral to advancing the field of surgery. Presently, a small cohort of medical students/residents successfully acquired and applied basic BME concepts in a relatively short period of time relative to other training paradigms. Our findings also suggest medical students recognize unmet needs in the hospital setting, and those who completed a BME course felt more able to take steps to meet those needs. Early integration of biomedical engineering principles in medical training may help produce more innovative and well-rounded surgeons.

  View details for DOI 10.1016/j.amjsurg.2022.11.018

  View details for PubMedID 36496271

• Paroxysmal Non-Kinesigenic Choreoathetosis Case Report and a Review of the Pathogenesis. Cureus Kara, R. H., Park, G., Lallani, S. B., Kesserwani, H. N. 2022; 14 (2): e21804

  Abstract

  Paroxysmal dyskinesias are a rare group of episodic movement disorders characterized by any combination of dystonia, chorea, and athetosis. Patients usually present early in life with episodes of variable frequency involving the limbs or facial muscles that can be disabling. In this article, we present a case of paroxysmal non-kinesigenic dyskinesia that was responsive to the sodium-channel blocker carbamazepine. Recent data has revealed the role of voltage-gated sodium channels in the pathophysiology of the disease; hence, these disorders are referred to as channelopathies. Further advancements in genetic analysis have elucidated targets corresponding to these disorders, indicating a possible role for gene sequencing in helping to differentiate the subtypes of paroxysmal dyskinesias. This case report sheds light on the pathophysiology of the various channelopathies, especially the findings of cerebellar spreading depolarization and its implication in paroxysmal kinesigenic and non-kinesigenic dyskinesias.

  View details for DOI 10.7759/cureus.21804

  View details for PubMedID 35251868

  View details for PubMedCentralID PMC8890460

• Use of an Intracranial Drain as a Conduit for Treatment of an Intracranial Streptococcus intermedius Abscess. Cureus Lallani, S. B., Hyte, M., Trieu, E., Reyes-Sacin, C., Doan, N. 2021; 13 (4): e14613

  Abstract

  Brain abscesses are difficult to manage clinically and often result in a poor outcome. Although surgical and medical therapeutics have progressed, there are still challenges that make treating intracranial abscesses problematic. One of these treatment barriers is the poor penetration of intravenous antibiotics to the infection source through the blood-brain barrier. In this case report, we will discuss the use of a surgical drain as a conduit for direct antibiotic administration for a rare, recurrent Streptococcus intermedius infection. This technique allows us to bypass the blood-brain barrier while also reducing the systemic effects of antibiotics. When used in conjunction with craniotomy and resection, direct antibiotic administration via a surgical drain proved to be effective at treating our patient's abscess and preventing recurrence.

  View details for DOI 10.7759/cureus.14613

  View details for PubMedID 34040913

  View details for PubMedCentralID PMC8139600

• YAP/TAZ Transcriptional Coactivators Create Therapeutic Vulnerability to Verteporfin in EGFR-mutant Glioblastoma. Clinical cancer research : an official journal of the American Association for Cancer Research Vigneswaran, K., Boyd, N. H., Oh, S. Y., Lallani, S., Boucher, A., Neill, S. G., Olson, J. J., Read, R. D. 2021; 27 (5): 1553-1569

  Abstract

  Glioblastomas (GBMs), neoplasms derived from glia and neuroglial progenitor cells, are the most common and lethal malignant primary brain tumors diagnosed in adults, with a median survival of 14 months. GBM tumorigenicity is often driven by genetic aberrations in receptor tyrosine kinases, such as amplification and mutation of EGFR.Using a Drosophila glioma model and human patient-derived GBM stem cells and xenograft models, we genetically and pharmacologically tested whether the YAP and TAZ transcription coactivators, effectors of the Hippo pathway that promote gene expression via TEA domain (TEAD) cofactors, are key drivers of GBM tumorigenicity downstream of oncogenic EGFR signaling.YAP and TAZ are highly expressed in EGFR-amplified/mutant human GBMs, and their knockdown in EGFR-amplified/mutant GBM cells inhibited proliferation and elicited apoptosis. Our results indicate that YAP/TAZ-TEAD directly regulates transcription of SOX2, C-MYC, and EGFR itself to create a feedforward loop to drive survival and proliferation of human GBM cells. Moreover, the benzoporphyrin derivative verteporfin, a disruptor of YAP/TAZ-TEAD-mediated transcription, preferentially induced apoptosis of cultured patient-derived EGFR-amplified/mutant GBM cells, suppressed expression of YAP/TAZ transcriptional targets, including EGFR, and conferred significant survival benefit in an orthotopic xenograft GBM model. Our efforts led us to design and initiate a phase 0 clinical trial of Visudyne, an FDA-approved liposomal formulation of verteporfin, where we used intraoperative fluorescence to observe verteporfin uptake into tumor cells in GBM tumors in human patients.Together, our data suggest that verteporfin is a promising therapeutic agent for EGFR-amplified and -mutant GBM.

  View details for DOI 10.1158/1078-0432.CCR-20-0018

  View details for PubMedID 33172899

  View details for PubMedCentralID PMC8440125

• Child Abuse: The Consequence of an Undiagnosed Giant Olfactory Groove Meningioma? Cureus Lallani, S. B., Adams, D., Doan, H., Trieu, E., Doan, N. 2021; 13 (2): e13582

  Abstract

  Olfactory groove meningiomas are slow-growing tumors that manifest with headaches, changes in vision, and personality changes. The anatomic location of these tumors makes psychiatric disturbances more common early in the stage of tumors than focal neurological deficits. The case study here describes a unique instance of an undiagnosed giant olfactory groove meningioma in a young mother who was charged with a felony of aggravated child abuse for the death of her toddler daughter. The patient underwent gross tumor resection and radiation therapy, which halted the visual decline, resolved the frontal headaches, and the patient showed improved mood. In this patient, the insidious onset of personality changes without obvious focal neurologic deficits until late as well as a history of depression likely contributed to the delayed diagnosis. Failure to notice these initial behavioral manifestations in these patients allows for further psychiatric and cognitive decline, which can result in devastating social consequences.

  View details for DOI 10.7759/cureus.13582

  View details for PubMedID 33796425

  View details for PubMedCentralID PMC8006209

• Therapeutic targeting of the YAP/TAZ pathway in glioblastoma with verteporfin Boyd, N. H., Vigneswaran, K., Lallani, S., Oh, S., Boucher, A., Olson, J., Read, R. AMER ASSOC CANCER RESEARCH. 2020

  View details for DOI 10.1158/1538-7445.AM2020-3789

  View details for Web of Science ID 000590059305338

• Upregulation of the chromatin remodeler HELLS is mediated by YAP1 in Sonic Hedgehog Medulloblastoma. Scientific reports Robinson, M. H., Maximov, V., Lallani, S., Farooq, H., Taylor, M. D., Read, R. D., Kenney, A. M. 2019; 9 (1): 13611

  Abstract

  Medulloblastoma is a malignant pediatric tumor that arises from neural progenitors in the cerebellum. Despite a five-year survival rate of ~70%, nearly all patients incur adverse side effects from current treatment strategies that drastically impact quality of life. Roughly one-third of medulloblastoma are driven by aberrant activation of the Sonic Hedgehog (SHH) signaling pathway. However, the scarcity of genetic mutations in medulloblastoma has led to investigation of other mechanisms contributing to cancer pathogenicity including epigenetic regulation of gene expression. Here, we show that Helicase, Lymphoid Specific (HELLS), a chromatin remodeler with epigenetic functions including DNA methylation and histone modification, is induced by Sonic Hedgehog (SHH) in SHH-dependent cerebellar progenitor cells and the developing murine cerebella. HELLS is also up-regulated in mouse and human SHH medulloblastoma. Others have shown that HELLS activity generally results in a repressive chromatin state. Our results demonstrate that increased expression of HELLS in our experimental systems is regulated by the oncogenic transcriptional regulator YAP1 downstream of Smoothened, the positive transducer of SHH signaling. Elucidation of HELLS as one of the downstream effectors of the SHH pathway may lead to novel targets for precision therapeutics with the promise of better outcomes for SHH medulloblastoma patients.

  View details for DOI 10.1038/s41598-019-50088-1

  View details for PubMedID 31541170

  View details for PubMedCentralID PMC6754407

• Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts. Scientific reports Stafman, L. L., Williams, A. P., Marayati, R., Aye, J. M., Markert, H. R., Garner, E. F., Quinn, C. H., Lallani, S. B., Stewart, J. E., Yoon, K. J., Whelan, K., Beierle, E. A. 2019; 9 (1): 13259

  Abstract

  Patient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neuroblastoma PDXs in vitro. Cells were treated with two small molecule inhibitors of FAK, PF-573,228 (PF) and 1,2,4,5-benzentetraamine tetrahydrochloride (Y15). Following FAK inhibition, cell survival and proliferation decreased significantly and cell cycle arrest was seen in both cell lines. Migration and invasion assays were used to determine the effect of FAK inhibition on cell motility, which decreased significantly in both cell lines in the presence of either inhibitor. Finally, tumor cell stemness following FAK inhibition was evaluated with extreme limiting dilution assays as well as with immunoblotting and quantitative real-time PCR for the expression of stem cell markers. FAK inhibition decreased formation of tumorspheres and resulted in a corresponding decrease in established stem cell markers. FAK inhibition decreased many characteristics of the malignant phenotype, including cancer stem cell like features in neuroblastoma PDXs, making FAK a candidate for further investigation as a potential target for neuroblastoma therapy.

  View details for DOI 10.1038/s41598-019-49853-z

  View details for PubMedID 31519958

  View details for PubMedCentralID PMC6744403

• Striatal Interneurons in Transgenic Nonhuman Primate Model of Huntington's Disease. Scientific reports Lallani, S. B., Villalba, R. M., Chen, Y., Smith, Y., Chan, A. W. 2019; 9 (1): 3528

  Abstract

  Huntington's disease is an autosomal dominant neurodegenerative disorder associated with progressive motor and cognitive impairments, and the expansion of a cysteine-adenine-guanine trinucleotide (polyglutamine) repeats in exon one of the human huntingtin gene. The pathology of the disease is characterized by a profound degeneration of striatal GABAergic projection neurons with relative sparing of interneurons accompanied with astrogliosis. Here, we describe the striatal pathology in two genotypically different transgenic HD monkeys that exhibit degrees of disease progression that resembled those seen in juvenile- (rHD1) and adult-onset (rHD7) HD. The caudate nucleus and putamen underwent severe neuronal loss in both animals, while the striatal volume was reduced only in rHD1, the most severely affected monkey. The number of GABAergic (calretinin- and parvalbumin-positive) and cholinergic interneurons was also reduced in most striatal regions of these two monkeys, but to variable degrees. Overall, the density of interneurons was increased in rHD1, but not in rHD7, suggesting a relative sparing of interneurons over projection neurons in the striatum of the most affected HD monkey. The neuropil of both the caudate nucleus and putamen was invaded with reactive astrocytes in rHD1, while astrogliosis was much less severe in rHD7 and absent from control. Combined with behavioral data collected from these monkeys, our findings further demonstrate that transgenic HD monkeys share similar disease patterns with HD patients, making them a highly reliable preclinical HD animal model.

  View details for DOI 10.1038/s41598-019-40165-w

  View details for PubMedID 30837611

  View details for PubMedCentralID PMC6401084