Abdelkader Daoud

Abdelkader Daoud

Medical University of South Carolina

H-index: 9

North America-United States

Abdelkader Daoud Information

University

Medical University of South Carolina

Position

___

Citations(all)

406

Citations(since 2020)

247

Cited By

245

hIndex(all)

9

hIndex(since 2020)

8

i10Index(all)

9

i10Index(since 2020)

7

Email

University Profile Page

Medical University of South Carolina

Abdelkader Daoud Skills & Research Interests

Cancer Biology

Pharmacology

Top articles of Abdelkader Daoud

Benchmarking organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs

Cystic Fibrosis (CF) is a life-shortening disease that is caused by mutations in the CFTR gene, a gene that is expressed in multiple organs. There are several primary tissue models of CF disease, including nasal epithelial cultures and rectal organoids, that are effective in reporting the potential efficacy of mutation-targeted therapies called CFTR modulators. However, there is the well-documented variation in tissue dependent, therapeutic response amongst CF patients, even those with the same CF-causing mutation. Hence, there is an interest in developing strategies for benchmarking therapeutic efficacy in different organs relative to isogenic controls. In this study, we evaluated the CFTR chloride channel response to the highly effective CFTR modulator: Trikafta, in CF patient specific, iPSC-derived colonic and airway cultures relative to mutation-corrected (non-CF) tissues from that same individual. We measured pharmacological rescue in both tissues, but interestingly, Trikafta treatment resulted in different levels of functional rescue in the two tissues relative to the relevant isogenic control. This proof-of-concept study lays the groundwork for future comparisons of patient-specific CF therapeutic responses in both pulmonary and extra-pulmonary systems.

Authors

Abdelkader Daoud,Sunny Xia,Onofrio Laselva,Jia Xin Jiang,Christine Bear

Journal

bioRxiv

Published Date

2024

Human Pluripotent Stem Cell Derived Organoids Reveal a Role for WNT Signaling in Dorsal-Ventral Patterning of the Hindgut

The cloaca is a transient structure that forms in the terminal hindgut giving rise to the rectum dorsally and the urogenital sinus ventrally. Similarly, human hindgut cultures derived from human pluripotent stem cells generate human colonic organoids (HCOs) which also contain co-developing urothelial tissue. In this study, our goal was to identify pathways involved in cloacal patterning and apply this to human hindgut cultures. RNA-seq data comparing dorsal versus ventral cloaca in e10.5 mice revealed that WNT signaling was elevated in the ventral versus dorsal cloaca. Inhibition of WNT signaling in hindgut cultures biased their differentiation towards a colorectal fate. WNT activation biased differentiation towards a urothelial fate, giving rise to human urothelial organoids (HUOs). HUOs contained cell types present in human urothelial tissue. Based on our results, we propose a mechanism whereby WNT signaling patterns the ventral cloaca, prior to cloacal septation, to give rise to the urogenital sinus.

Authors

Na Qu,Abdelkader Daoud,Daniel O Kechele,Jorge O Munera

Journal

bioRxiv

Published Date

2024

Special AT-rich sequence-binding protein 2 (SATB2) represses proximal small intestine identity in human pluripotent stem cell derived ileal and colonic organoids

Background: Intestinal regional specification describes a process through which unique morphology and function are imparted to defined areas of the developing gastrointestinal (GI) tract. Human intestinal organoids can be generated from human pluripotent stem cells and patterned into distinct intestinal regions including duodenum, ileum and colon. Ileal and colonic organoids express epithelial Special AT-rich sequence-binding protein 2 (SATB2) and generate cell types specific to distinct intestinal regions. SATB2 is the earliest known transcription factor to be specifically expressed in the developing ileal and colonic epithelium in mice. However, the role of SATB2 in regional specification of ileal and colonic organoids has not been determined. The objective of this study was to determine if SATB2 is necessary for establishment of ileal and colonic epithelial identity in organoids. We hypothesized that SATB2 …

Authors

Na Qu,Abdelkader Daoud,Jorge Munera

Published Date

2023/5/23

Identification of novel substrates of the UBR5 E3 ubiquitin ligase in ovarian cancer

The ubiquitin proteasome system regulates the degradation of proteins in order to maintain cellular homeostasis, which is often disrupted in cancer cells. The UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5) protein is an E3 ubiquitin ligase that catalyzes the direct ubiquitination of protein substrates, most often resulting in substrate protein degradation. UBR5 is the human homolog of the Drosophilia hyperplastic discs (hyd) tumor suppressor gene. However, ubr5 is amplified and over-expressed in human ovarian and breast cancers, among others, and thought to play more of a tumor-promoting role in cancer. We previously demonstrated that targeting UBR5 expression in human ovarian cancer xenografts in mice with liposomal delivery of UBR5 siRNA inhibited tumor growth and sensitized tumors to the DNA-damaging agent cisplatin. To identify novel substrates of UBR5-stimulated degradation, we …

Authors

Scott T Eblen,Jennifer R Bethard,D Ralph Rogers,Abdelkader Daoud,Lalima K Madan,Lauren E Ball

Journal

Cancer Research

Published Date

2023/4/4

SMAD1 Is Dispensable for CDX2 Induction but Required for the Repression of Ectopic Small-Intestinal Gene Expression in Human-Pluripotent-Stem-Cell-Derived Colonic Organoids

The generation of gastrointestinal tissues from human pluripotent stem cells has provided unprecedented insight into the molecular mechanisms that drive the patterning of the primitive gut tube. Previous work has identified bone-morphogenetic-protein (BMP) signaling as an important mediator of mid/hindgut versus foregut and hindgut versus midgut cell fate choice. Inhibition of BMP signaling during gut tube morphogenesis inhibits the expression of the pan-intestinal transcription factor CDX2. Treatment of CDX2+ mid/hindgut cultures with BMP patterns them into hindgut, which gives rise to colonic organoids (HCOs). While the role for BMP signaling is clear, the molecular mechanisms through which BMP signaling patterns the mid/hindgut and colon remain unclear. BMPs bind to BMP receptors, activating a signaling cascade that results in the activation of SMADs, which function as transcription factors. We hypothesized that one of these factors, SMAD1, would be necessary for establishing the CDX2 domain and the colon domain. Unexpectedly, endoderm derived from SMAD1-deficient induced pluripotent stem cells was capable of inducing CDX2 in response to WNT and FGF signaling. In addition, CDX2+ gut tube cultures could activate posterior HOX genes in response to BMP. However, examination of HCOs following cytodifferentiation revealed that SMAD1-deficient HCOs ectopically expressed small-intestinal markers despite expressing posterior HOX genes. These results indicate that there is redundancy of SMADs during early hindgut patterning but that SMAD1 is required for the inhibition of small-intestinal gene expression in HCOs.

Authors

Na Qu,Abdelkader Daoud,Braxton Jeffcoat,Jorge O Múnera

Journal

Organoids

Published Date

2023/11/14

Generation, maintenance, and characterization of human pluripotent stem cell-derived intestinal and colonic organoids

Intestinal regional specification describes a process through which unique morphology and function are imparted to defined areas of the developing gastrointestinal (GI) tract. Regional specification in the intestine is driven by multiple developmental pathways, including the bone morphogenetic protein (BMP) pathway. Based on normal regional specification, a method to generate human colonic organoids (HCOs) from human pluripotent stem cells (hPSCs), which include human embryonic stem cells (hES) and induced pluripotent stem cells (iPSCs), was developed. A three-day induction of BMP signaling sufficiently patterns mid/hindgut tube cultures into special AT-rich sequence-binding protein 2 (SATB2)-expressing HCOs containing all of the main epithelial cell types present in human colon as well as co-developing mesenchymal cells. Omission of BMP (or addition of the BMP inhibitor NOGGIN) during this …

Authors

Na Qu,Abdelkader Daoud,Braxton Jeffcoat,Jorge O Múnera

Journal

JoVE (Journal of Visualized Experiments)

Published Date

2021/7/9

Low dose cyclophosphamide modulates tumor microenvironment by TGF-β signaling pathway

The tumor microenvironment has been recently recognized as a critical contributor to cancer progression and anticancer therapy-resistance. Cyclophosphamide (CTX) is a cytotoxic agent commonly used in clinics for the treatment of cancer. Previous reports demonstrated that CTX given at low continuous doses, known as metronomic schedule, mainly targets endothelial cells and circulating Tregs with unknown mechanisms. Here, we investigated the antitumor activity of two different metronomic schedules of CTX along with their corresponding MTD regimen and further explored their effect on immune function and tumor microenvironment. Toxicity evaluation was monitored by overall survival rate, weight loss, and histopathological analysis. A nude mouse model of Lewis lung cancer was established to assess the anti-metastatic effects of CTX in vivo. CD4+, CD8+, and CD4+CD25+FoxP3 T cells were selected by flow cytometry analysis. Low and continuous administration of CTX was able to restore immune function via increase of CD4+/CD8+ T cells and depletion of T regulatory cells, not only in circulatory and splenic compartments, but also at the tumor site. Low-dose CTX also reduced myofibroblasts, accompanied with an increased level of E-cadherin and low N-cadherin, both in the primary tumor and lung through the TGF-β pathway by the downregulated expression of TGF-β receptor 2. Our data may indicate that several other molecular mechanisms of CTX for tumor may be involved in metronomic chemotherapy, besides targeting angiogenesis and regulatory T cells.

Authors

Hui Zhong,Yifan Lai,Rui Zhang,Abdelkader Daoud,Qingyuan Feng,Jia Zhou,Jing Shang

Journal

International Journal of Molecular Sciences

Published Date

2020/1/31

Generation of human colonic organoids from human pluripotent stem cells

Advances in human pluripotent stem cell (hPSC) biology now allow the generation of organoids that resemble different regions of the gastrointestinal tract. Generation of region-specific organoids has been facilitated by developmental biology studies carried out in model organisms such as mouse, frog and chick. By mimicking embryonic development, hPSC-derived human colonic organoids (HCOs) can be generated through a stepwise differentiation, first into definitive endoderm (DE), then into mid/hindgut spheroids which are then patterned into posterior gut tissue which gives rise to HCOs following prolonged in vitro culture. HCOs undergo transitions similar to those observed in the developing colon of model organisms and human embryos. HCOs develop into tissue that resembles fetal colon on the basis of morphology, gene expression and presence of differentiated cell types. Generation of HCOs without the …

Authors

Abdelkader Daoud,Jorge O Múnera

Published Date

2020/1/1

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Abdelkader Daoud FAQs

What is Abdelkader Daoud's h-index at Medical University of South Carolina?

The h-index of Abdelkader Daoud has been 8 since 2020 and 9 in total.

What are Abdelkader Daoud's top articles?

The articles with the titles of

Benchmarking organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs

Human Pluripotent Stem Cell Derived Organoids Reveal a Role for WNT Signaling in Dorsal-Ventral Patterning of the Hindgut

Special AT-rich sequence-binding protein 2 (SATB2) represses proximal small intestine identity in human pluripotent stem cell derived ileal and colonic organoids

Identification of novel substrates of the UBR5 E3 ubiquitin ligase in ovarian cancer

SMAD1 Is Dispensable for CDX2 Induction but Required for the Repression of Ectopic Small-Intestinal Gene Expression in Human-Pluripotent-Stem-Cell-Derived Colonic Organoids

Generation, maintenance, and characterization of human pluripotent stem cell-derived intestinal and colonic organoids

Low dose cyclophosphamide modulates tumor microenvironment by TGF-β signaling pathway

Generation of human colonic organoids from human pluripotent stem cells

are the top articles of Abdelkader Daoud at Medical University of South Carolina.

What are Abdelkader Daoud's research interests?

The research interests of Abdelkader Daoud are: Cancer Biology, Pharmacology

What is Abdelkader Daoud's total number of citations?

Abdelkader Daoud has 406 citations in total.

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