Sharif Moradi Ph.D.

Department of Stem Cells and Developmental Biology

Assistant professor

Email: sharif.moradi@royaninstitute.org

Phone: +98 21 23562512

CV: Dr. Sharif Moradi

Sharif Moradi got his BSc in Plant Biology from Khwarizmi University of Tehran in 2008 and his MSc in Cell & Molecular Biology from Tehran University in 2010. During his master, he utilized an explant culture to cultivate, and analyze the expression of two glaucoma-related proteins FOXC1 and PITX2 in, human trabecular meshwork cells that are located around the base of the cornea, near the ciliary body. He then joined Royan Institute as a PhD student of Developmental Biology and worked in Prof. Hossein Baharvand’s lab to analyze the expression and functional significance of microRNAs in ES and iPS cells. In 2014, he moved to Germany and worked for one year in Prof. Thomas Braun’s lab at Max-Planck Institute (Bad Nauheim) to do microRNA functional analyses in ES cell self-renewal as well as microRNA expression profiling during ES cell derivation from murine blastocysts. He got his PhD in 2017 and is now an assistant professor at Royan Institute, focusing on non-coding RNAs especially microRNAs in immortal cells (ES and iPS cells as well as cancer cells). He is particularly interested in developing diagnostic tools and therapeutic strategies against cancer using non-coding RNAs.

Our focus is on two research areas that are somewhat related to each other: pluripotency and tumorigenicity. The interface of these two phenomena is immortality: pluripotency represents normal immortality in vitro (pluripotency exists only transiently in vivo), whereas tumorigenesis is the abnormal, uncontrolled proliferation of cancer cells both in vitro and in vivo.

Pluripotency

We are interested to figure out the mechanisms underlying the immortality of pluripotent stem cells (PSCs), i.e. embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in order to exploit the obtained knowledge for efficient and safe generation of PSCs for potential regenerative medicine applications in future. Our mechanistic studies are focused on microRNA and lncRNA biology as well as small-molecule-based alterations in gene expression. Therefore, we aim to derive safe PSCs using small molecules and microRNAs to eliminate the need to use viruses and/or genomic integration. We also aim at generating safe iPSCs with high efficiency, since safe approaches to iPSC reprogramming usually suffer from extremely low efficiencies. We are also working on pre-implantation embryogenesis, as PSCs are present in embryos only during this time window. Notably, although PSCs hold great promise in regenerative medicine, the residual PSCs within the PSC-derived differentiated cell population might lead to tumor formation in patient in long term. We are currently developing strategies to remove tumorigenic PSCs from the differentiated cell populations in order to ensure the safety of PSC-based cell-replacement therapies.

 

Tumorigenicity

Our research on PSCs and their tumorigenic potential along with the fact that we all are witnessing how a large number of people and especially our dearest and nearest people die of cancer, encouraged us to start focusing on tumors and cancers as a top priority. In Iran, cancer has had an increasing incidence and mortality rate in recent years. In Iranian men, stomach cancer, and in Iranian women, breast cancer constitute the most prevalent cancers. We are starting to focus on these cancer types as they are also highly prevalent and deadly in other ethnicities and societies as well. Since cancers related to digestive tract are more common in Iran, we have put more focus on these types of cancers, particularly gastric and esophageal cancers. We want to fight cancers using two main approaches:

Early cancer diagnosis

The majority of cancers, including digestive tract cancers, are diagnosed only when the tumor has grown into a large size and metastasized to other parts of the patient’s body. In such situations, it is often too late for the clinicians to be able to effectively help cancer patients. Patients with esophageal cancer, for example, mostly die within 1 year of diagnosis, because the cancer is usually not detected in an early stage. The benefit of early detection of cancer is that it remarkably enhances the chances for successful treatments in an early stage, thereby saving many lives. One of our important missions is to try to detect cancers in an early stage through finding early biomarkers, such as circulating microRNAs, in body fluids. To this end, we are trying to develop biosensors for fast, sensitive, and specific biomarker detection. Our plan is to bring biosensors to the bedside for potential point-of-care testing. Effective point-of-care testing will lead to more successful cancer therapy.

 

Cancer therapy

The majority of cancers are currently not diagnosed in an early stage or are too difficult to be effectively targeted, and therefore kill many patients. Current strategies appear to be ineffective or less efficient, since there is currently a high rate of cancer mortality worldwide. To kill cancer cells, we are interested in using targeted therapies and combinatorial therapeutic approaches exploiting the potential of microRNAs and siRNAs along with small molecules modulating RNAi and other pathways. We are also interested to use natural compounds along with other regimens to increase the chances for successful therapy. Cancers are too complicated and we need to understand the biology of cancer cells more accurately. We are also highly interested to investigate the mechanisms of cancer development and metastasis. We hope that our collective efforts contribute to making a world with less pain and more happiness in the future.

MSc Student:

Samira Soori, MSc student

Project: Functional analysis of microRNAs during embryonic stem cell derivation

Amir Mokhlesi, MSc student

Project: Discovery of key microRNAs for treating gastric cancer

Fahimeh Shirzadeh, MSc student

Project: MicroRNA-assisted transdifferentiation of fibroblasts into renal epithelial cells

Rana Bagheri, MSc student

Project: Elimination of residual pluripotent cells from differentiated cell populations using small molecules

Parisa Torabi, MSc student

Project: Effective targeting of esophageal cancer using a combinatorial approach

Selected Publications:

Seyedeh-Nafiseh Hassani*, Sharif Moradi*, Sara Taleahmad, Thomas Braun, Hossein Baharvand. Transition of inner cell mass to embryonic stem cells: mechanisms, facts, and hypotheses. Cellular & Molecular Life Sciences, 2018

 

* Co-first authors

 

Sharif Moradi, Thomas Braun, Hossein Baharvand. miR-302b-3p promotes self-renewal properties in LIF-withdrawn embryonic stem cells. Cell Journal (Yakhteh), 2018 

 

Sharif Moradi, Ali Sharifi-Zarchi, Amirhossein Ahmadi, Sepideh Mollamohammadi, Alexander Stubenvoll, Stefan Günther, Ghasem Hosseini Salekdeh, Sassan Asgari, Thomas Braun, Hossein Baharvand. Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground State Pluripotency. Stem Cell Reports, 2017

 

Ebrahim Shahbazi, Sharif Moradi, Shiva Nemati, Leila Satarian, Mohsen Basiri, Hamid Gourabi, Narges Zare Mehrjardi, Patrick Günther, Angelika Lampert, Kristian Händler, Firuze Fulya Hatay, Diana Schmidt, Marek Molcanyi, Jürgen Hescheler, Joachim L. Schultze, Tomo Saric, Hossein Baharvand. Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor. Stem Cell Reports, 2016

 

Sharif Moradi, Sassan Asgari, Hossein Baharvand. Concise review: harmonies played by microRNAs in cell fate reprogramming

. Stem Cells, 2014

 

Seyedeh-Nafiseh Hassani, Mehdi Totonchi, Ali Sharifi-Zarchi, Sepideh Mollamohammadi, Mohammad Pakzad, Sharif Moradi, Azam Samadian, Najmehsadat Masoudi, Shahab Mirshahvaladi, Ali Farrokhi, Boris Greber, Marcos J. Araúzo-Bravo, Davood Sabour, Mehdi Sadeghi, Ghasem Hosseini Salekdeh, Hamid Gourabi, Hans R. Schöler, Hossein Baharvand. Inhibition of TGFβ Signaling Promotes Ground State Pluripotency. Stem Cell Reviews and Reports, 2014

 

Sharif Moradi, Hossein Baharvand. Induced pluripotent stem cells, from generation to application

. Tehran University Medical Journal, 2014

Dr. Moradi’s lab is focused on the expression and functional analysis of non-coding RNAs in immortal cells (i.e. pluripotent and cancer cells) as well as on developing diagnostic tools and therapeutic strategies using non-coding RNAs (e.g. miRNAs, siRNAs, and lncRNAs). We are accepting talented MSc and PhD students interested in these areas of research. Please have a look at our Open Position

Dr. Moradi’s lab is focused on the expression and functional analysis of non-coding RNAs in immortal cells (i.e. pluripotent and cancer cells) as well as on developing diagnostic tools and therapeutic strategies using non-coding RNAs (e.g. miRNAs, siRNAs, and lncRNAs). We are accepting MSc and PhD students interested in these interesting areas of research.

Interested and talented students are invited to send their requests along with their CV to sharif.moradi@gmail.com.