Howard University Graduate School

HUGS Research Magazine
and Graduate School Research Archive

INTERVIEWIssue 016

Professor Hassan Ashktorab and International Group of Scientists Conducting Research on Gastrointestinal Diseases

By Gwendolyn S. Bethea, Ph.D.


Colon Cancer Diagram


Hassan Ashktorab

Hassan Ashktorab, Ph.D., Professor in the Department of Medicine and Director of Microarray in the Howard University Cancer recently answered questions pertaining to his research on gastrointestinal polyps and cancer detection.

Q: What was the purpose of your research?
H. Ashktorab: Our group is working on genetics, epigenetics, microbiomics and epidemiological outcome research in gastrointestinal diseases. Optical visualization for colonoscopy is part of the outcome and technology in gastrointestinal polyp and cancer detection. There are different endoscopes in terms of their resolutions. High definition (HD) colonoscopy with Narrow Band Imaging (NBI) scope has the advantage to detect vascular or mucosal characteristics so that any abnormal growth could be better visualized and diagnosed when compared to standard (ST) colonoscopy. The higher the resolution the better detection of the lesion will be. Therefore, we aimed to study the accuracy of using HD scope with NBI vs. standard white light colonoscopy without NBI (ST), to predict the histology of colon polyps, particularly those < 1 cm at Howard University Hospital, Gastroenterology Division.

Q: Was it predictive in any way in terms of incidence of colorectal cancer or polyps among African Americans, particularly African American men?
H. Ashktorab: African Americans in general have high incidence of both colon polyps and cancer compared to the general population. We have published several papers and indicated based on the Howard University hospital data and other US data, that both males and females have higher rates of colon neoplasia. However, females are slightly more affected in our study cohort.

Q: Did you collaborate with other schools/colleges in the US and abroad?
H. Ashktorab: : We have very active collaborations inside Howard University, outside the District of Columbia, in the United States and around the world. Our group has a long history of collaboration at Howard University within Cancer center and outside the College of Medicine. As a result, we have published many interesting and significant studies in gastrointestinal tract including esophageal, stomach, colon and liver diseases. Some of these gastrointestinal research studies cover North America, Asia, and Europe.

Q: Do you have preliminary data as to what environmental and genetic factors play an important role in the disparity of colorectal disease in African Americans?
H. Ashktorab: Low social economic status including education, housing, income, access to health care, lack of follow up and diet are major environmental factors. Physical activities are also a major part of the behavioral factors. Genetic factors has low, moderate and high categories. These may include family history and type of genetic defects.

Q: Can you name some of the schools in other countries with which you have collaborated?
H. Ashktorab: We had collaborations with Korea in eight publications as listed below.

https://www.ncbi.nlm.nih.gov/pubmed/?term=ashktorab+And+korea:

Gastrokine 1 inhibits gastrin-induced cell proliferation. Kim O, Yoon JH, Choi WS, Ashktorab H, Smoot DT, Nam SW, Lee JY, Park WS. Gastric Cancer. 2016 Apr;19(2):381-91. doi: 10.1007/s10120-015-0483-2. PMID:25752269

Gastrokine 1 inhibits the carcinogenic potentials of Helicobacter pylori CagA. Yoon JH, Seo HS, Choi SS, Chae HS, Choi WS, Kim O, Ashktorab H, Smoot DT, Nam SW, Lee JY, Park WS. Carcinogenesis. 2014 Nov;35(11):2619-29. doi: 10.1093/carcin/bgu199. PMID:25239641

nc886, a non-coding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer. Lee KS, Park JL, Lee K, Richardson LE, Johnson BH, Lee HS, Lee JS, Kim SB, Kwon OH, Song KS, Kim YS, Ashktorab H, Smoot DT, Jeon SH, Kim SY, Lee YS. Oncotarget. 2014 Jun 15;5(11):3944-55. PMID:25003254

The effect of Helicobacter pylori CagA on the HER-2 copy number and expression in gastric cancer. Shim JH, Yoon JH, Choi SS, Ashktorab H, Smoot DT, Song KY, Nam SW, Lee JY, Park CH, Park WS. Gene. 2014 Aug 10;546(2):288-96. doi: 10.1016/j.gene.2014.05.064. PMID:24879917

MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer. Shin JY, Kim YI, Cho SJ, Lee MK, Kook MC, Lee JH, Lee SS, Ashktorab H, Smoot DT, Ryu KW, Kim YW, Choi IJ. PLoS One. 2014 Jan 21;9(1):e85205. doi: 10.1371/journal.pone.0085205. PMID:24465504

GKN2 contributes to the homeostasis of gastric mucosa by inhibiting GKN1 activity. Kim O, Yoon JH, Choi WS, Ashktorab H, Smoot DT, Nam SW, Lee JY, Park WS. J Cell Physiol. 2014 Jun;229(6):762-71. doi: 10.1002/jcp.24496. PMID:24151046

GKN1-miR-185-DNMT1 axis suppresses gastric carcinogenesis through regulation of epigenetic alteration and cell cycle. Yoon JH, Choi YJ, Choi WS, Ashktorab H, Smoot DT, Nam SW, Lee JY, Park WS. Clin Cancer Res. 2013 Sep 1;19(17):4599-610. doi: 10.1158/1078-0432.CCR-12-3675. PMID:23846337

Gastrokine 1 regulates NF-?B signaling pathway and cytokine expression in gastric cancers. Yoon JH, Cho ML, Choi YJ, Back JY, Park MK, Lee SW, Choi BJ, Ashktorab H, Smoot DT, Nam SW, Lee JY, Park WS. J Cell Biochem. 2013 Aug;114(8):1800-9. doi: 10.1002/jcb.24524. PMID:23444260

We had collaborations with Italy and in the following publications:

SEL1L, an UPR response protein, a potential marker of colonic cell transformation. Ashktorab H, Green W, Finzi G, Sessa F, Nouraie M, Lee EL, Morgano A, Moschetta A, Cattaneo M, Mariani-Costantini R, Brim H, Biunno I. Dig Dis Sci. 2012 Apr;57(4):905-12. doi: 10.1007/s10620-011-2026-y. PMID:22350780

We had collaborations with the prestigious Max-Delbruck center in Germany in the following publication found at this link https://www.ncbi.nlm.nih.gov/pubmed/?term=ashktorab+And+germany

J Transl Med. 2016 Jul 20;14(1):215. doi: 10.1186/s12967-016-0971-0. Increased MACC1 levels in tissues and blood identify colon adenoma patients at high risk. Ashktorab H1, Hermann P2, Nouraie M3, Shokrani B4, Lee E4, Haidary T3, Brim H5, Stein U6,7. Author information 1Department of Medicine and Cancer Center, Howard University, 2041 Georgia Avenue NW, Washington, DC, 20059, USA. hashktorab@howard.edu. 2Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strabe 10, 13125, Berlin, Germany.

We had collaborations with India in the publications below.

https://www.ncbi.nlm.nih.gov/pubmed/?term=ashktorab+And+india:

Inhibition of histone/lysine acetyltransferase activity kills CoCl2-treated and hypoxia-exposed gastric cancer cells and reduces their invasiveness. Rath S, Das L, Kokate SB, Ghosh N, Dixit P, Rout N, Singh SP, Chattopadhyay S, Ashktorab H, Smoot DT, Swamy MM, Kundu TK, Crowe SE, Bhattacharyya A. Int J Biochem Cell Biol. 2017 Jan;82:28-40. doi: 10.1016/j.biocel.2016.11.014. PMID:27890795

SILAC-based quantitative proteomic analysis of gastric cancer secretome. Marimuthu A, Subbannayya Y, Sahasrabuddhe NA, Balakrishnan L, Syed N, Sekhar NR, Katte TV, Pinto SM, Srikanth SM, Kumar P, Pawar H, Kashyap MK, Maharudraiah J, Ashktorab H, Smoot DT, Ramaswamy G, Kumar RV, Cheng Y, Meltzer SJ, Roa JC, Chaerkady R, Prasad TS, Harsha HC, Chatterjee A, Pandey A. Proteomics Clin Appl. 2013 Jun;7(5-6):355-66. doi: 10.1002/prca.201200069.

We had collaborations with China in the following publications:

https://www.ncbi.nlm.nih.gov/pubmed/?term=ashktorab+And+china

MicroRNA-211 expression promotes colorectal cancer cell growth in vitro and in vivo by targeting tumor suppressor CHD5. Cai C, Ashktorab H, Pang X, Zhao Y, Sha W, Liu Y, Gu X. PLoS One. 2012;7(1):e29750. doi: 10.1371/journal.pone.0029750. PMID:22235338

The impact of C-MYC gene expression on gastric cancer cell. Zhang L, Hou Y, Ashktorab H, Gao L, Xu Y, Wu K, Zhai J, Zhang L. Mol Cell Biochem. 2010 Nov;344(1-2):125-35. doi: 10.1007/s11010-010-0536-0. PMID:20737197

We had collaborations with Saudi Arabia in the publications below.

https://www.ncbi.nlm.nih.gov/pubmed/?term=ashktorab+And+suadi

Gastroenterol Res Pract. 2016;2016:2102674. doi: 10.1155/2016/2102674. Epub 2016 Sep 1. Reduced Representation Bisulfite Sequencing Determination of Distinctive DNA Hypermethylated Genes in the Progression to Colon Cancer in African Americans. Ashktorab H1, Shakoori A2, Zarnogi S3, Sun X4, Varma S5, Lee E6, Shokrani B6, Laiyemo AO1, Washington K3, Brim H6.

We had collaborations with Oman in the following publications:

Sporadic colon cancer: mismatch repair immunohistochemistry and microsatellite instability in Omani subjects. Ashktorab H, Brim H, Al-Riyami M, Date A, Al-Mawaly K, Kashoub M, Al-Mjeni R, Smoot DT, Al-Moundhri M, Al-Hashemi S, Ganguly SS, Raeburn S. Dig Dis Sci. 2008 Oct;53(10):2723-31. doi: 10.1007/s10620-007-0189-3. PMID:18299982

We had collaborations with Singapore in the following publications:

https://www.ncbi.nlm.nih.gov/pubmed/?term=ashktorab+And+singapore

A role for RUNX3 in inflammation-induced expression of IL23A in gastric epithelial cells. Hor YT, Voon DC, Koo JK, Wang H, Lau WM, Ashktorab H, Chan SL, Ito Y. Cell Rep. 2014 Jul 10;8(1):50-8. doi: 10.1016/j.celrep.2014.06.003. PMID:25008775

Discovery of SLC3A2 cell membrane protein as a potential gastric cancer biomarker: implications in molecular imaging. Yang Y, Toy W, Choong LY, Hou P, Ashktorab H, Smoot DT, Yeoh KG, Lim YP. J Proteome Res. 2012 Dec 7;11(12):5736-47. doi: 10.1021/pr300555y. PMID:23116296

Isorhamnetin inhibits proliferation and invasion and induces apoptosis through the modulation of peroxisome proliferator-activated receptor ? activation pathway in gastric cancer. Ramachandran L, Manu KA, Shanmugam MK, Li F, Siveen KS, Vali S, Kapoor S, Abbasi T, Surana R, Smoot DT, Ashktorab H, Tan P, Ahn KS, Yap CW, Kumar AP, Sethi G. J Biol Chem. 2012 Nov 2;287(45):38028-40. doi: 10.1074/jbc.M112.388702. Erratum in: J Biol Chem. 2013 Jun 28;288(26):18777. PMID:22992727

CD44-SLC1A2 gene fusions in gastric cancer. Tao J, Deng NT, Ramnarayanan K, Huang B, Oh HK, Leong SH, Lim SS, Tan IB, Ooi CH, Wu J, Lee M, Zhang S, Rha SY, Chung HC, Smoot DT, Ashktorab H, Kon OL, Cacheux V, Yap C, Palanisamy N, Tan P. Sci Transl Med. 2011 Apr 6;3(77):77ra30. doi: 10.1126/scitranslmed.3001423. PMID:21471434

Cathepsin S mediates gastric cancer cell migration and invasion via a putative network of metastasis-associated proteins. Yang Y, Lim SK, Choong LY, Lee H, Chen Y, Chong PK, Ashktorab H, Wang TT, Salto-Tellez M, Yeoh KG, Lim YP. J Proteome Res. 2010 Sep 3;9(9):4767-78. doi: 10.1021/pr100492x. Erratum in: J Proteome Res. 2010 Dec 3;9(12):6801. muliple author names corrected. PMID:20812763

Upregulation of plasma C9 protein in gastric cancer patients. Chong PK, Lee H, Loh MC, Choong LY, Lin Q, So JB, Lim KH, Soo RA, Yong WP, Chan SP, Smoot DT, Ashktorab H, Yeoh KG, Lim YP. Proteomics. 2010 Sep;10(18):3210-21. doi: 10.1002/pmic.201000127. PMID:20707004

ITIH3 is a potential biomarker for early detection of gastric cancer. Chong PK, Lee H, Zhou J, Liu SC, Loh MC, Wang TT, Chan SP, Smoot DT, Ashktorab H, So JB, Lim KH, Yeoh KG, Lim YP. J Proteome Res. 2010 Jul 2;9(7):3671-9. doi: 10.1021/pr100192h. PMID:20515073

We had collaborations with Hong Kong in the following publications:

https://www.ncbi.nlm.nih.gov/pubmed/?term=ashktorab+And+Hong+Kong

Clin Cancer Res. 2016 Oct 3. pii: clincanres.1599.2016. [Epub ahead of print] Fecal Bacteria Act as Novel Biomarkers for Non-Invasive Diagnosis of Colorectal Cancer. Liang JQ1, Chiu J2, Chen Y3, Huang Y4, Higashimori A5, Fang JY6, Brim H7, Ashktorab H7, Ng SC8, Ng SS9, Zheng S4, Chan FK10, Sung JJ11, Yu J12.

We had collaboration with Iran in the publications below.

Targeted exome sequencing reveals distinct pathogenic variants in Iranians with colorectal cancer. Ashktorab H, Mokarram P, Azimi H, Olumi H, Varma S, Nickerson ML, Brim H. Oncotarget. 2016 Dec 16. doi: 10.18632/oncotarget.13977. [Epub ahead of print] PMID:28002797

An integrative CGH, MSI and candidate genes methylation analysis of colorectal tumors. Brim H, Abu-Asab MS, Nouraie M, Salazar J, Deleo J, Razjouyan H, Mokarram P, Schaffer AA, Naghibhossaini F, Ashktorab H. PLoS One. 2014 Jan 27;9(1):e82185. doi: 10.1371/journal.pone.0082185. PMID:24475022

Distinct high-profile methylated genes in colorectal cancer. Mokarram P, Kumar K, Brim H, Naghibalhossaini F, Saberi-firoozi M, Nouraie M, Green R, Lee E, Smoot DT, Ashktorab H. PLoS One. 2009 Sep 11;4(9):e7012. doi: 10.1371/journal.pone.0007012. PMID:19750230

Impact of BRAF, MLH1 on the incidence of microsatellite instability high colorectal cancer in populations based study. Brim H, Mokarram P, Naghibalhossaini F, Saberi-Firoozi M, Al-Mandhari M, Al-Mawaly K, Al-Mjeni R, Al-Sayegh A, Raeburn S, Lee E, Giardiello F, Smoot DT, Vilkin A, Boland CR, Goel A, Hafezi M, Nouraie M, Ashktorab H. Mol Cancer. 2008 Aug 21;7:68. doi: 10.1186/1476-4598-7-68. PMID:18718023

Siavoshi F, Malekzadeh R, Daneshmand M, Ashktorab H. Dig Dis Sci. 2005 Nov;50(11):2075-80. PMID:16240218

Q: Can you provide a link to some of the research articles on this subject area?
H. Ashktorab: For a more complete list please see: https://www.ncbi.nlm.nih.gov/pubmed/?term=Ashktorab%2C+hassan

We have also published book chapters.

Our gastrointestinal genetic, epigenetic, microbiome and outcome research group at Howard including Dr. Brim and other faculty members, graduate students, medical students, post-doc, residents, and fellows have made major contribution in all of the above publications. Of course our international contributors were part of our team work.

Q: How were students involved in your research?
H. Ashktorab: We have enjoyed supervising graduate, undergraduate, medical students, residents and gastroenterology fellows. Our laboratory has a policy for graduate students' mentorship and supervision. One of the criteria is after the graduate student agrees to work with our group, then if they are in Masters program they have to publish one peer review paper for their thesis research study before graduation. If they are in the Ph.D. program, they have to publish two papers for their dissertation research work. We have been successful in this research publication policy and all of our students have published their research studies. All of the graduate students who joined our lab for either the master's or Ph.D. research work have already published high impact articles in the gastrointestinal disease field.

Q: I note that the first study of this kind was conducted in Japan, with results being a significant difference between the researched populations, and that your study yielded no significant difference among the researched populations. To what do you attribute the difference in results between the Japan-based study and your study?
H. Ashktorab: The optical diagnosis is based on the technology and the technology does not discriminate between disease based on race or ethnicity. Therefore, we did not expect or had any intention to compare the races with the optical diagnosis using standard scope with or without narrow banding to high definition scope.

Q: What are the next steps in your research?
H. Ashktorab: We would like to integrate technology and biomarker discovery for the prediction and prognosis of gastrointestinal diseases specifically in African Americans. Our group has introduced several novel and distinctive genetic, epigenetics and gut microbiome markers in colon neoplasia in African Americans. We will continue our research to elucidate environmental and genetic factors that play an important role in disparity of colorectal disease in African Americans.

Thank you.

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