Mission Statement

Lab 2022

The Mostoslavsky Lab is a basic science laboratory in the Section of Gastroenterology in the Department of Medicine at Boston University, affiliated with the Boston University Center for Regenerative Medicine (CReM). Our goal is to study human biology in normal and disease states, through the use of stem cells in general and pluripotent stem cells in particular, with major focuses on gastrointestinal tract, neurodegeneration caused by prion diseases and immunity/inflammation. We believe that by discovering the mechanisms involved in stem cell self-renewal and differentiation we will be able to manipulate stem cell fate and use it as the basis for the correction of several diseases. Taking advantage of our long history of genetic manipulation, we are using gene editing techniques (such as CRISPR based editing) to generate a variety of reporter lines as well as isogenic mutant vs corrected iPSC lines for the study of lineage specification as well as disease modeling.

The Principal Investigator

Gustavo Mostoslavsky, MD PhD

Dr. Mostoslavsky

Dr. Mostoslavsky received his MD from the University of Tucuman in Argentina and his PhD from the Hebrew University in Jerusalem, Israel. His longstanding interest in basic science and regenerative medicine brought him to Harvard Medical School to pursue postdoctoral studies with stem cells and gene therapy. In 2008 Dr. Mostoslavsky opened his own lab at Boston University. He is currently Professor of Medicine in the Section of Gastroenterology in the Department of Medicine at Boston University School of Medicine. His main research interests are stem cells, disease modeling, regenerative medicine, gene correction and lentiviral vectors as tools for gene transfer. Dr. Mostoslavsky is a founder and Co-Director of the BU Center for Regenerative Medicine (CReM).

Areas of Research

st8-d12

iPS cells

Our lab has a major interest in the study of induced Pluripotent Stem cells or iPS cells and the development of tools for their generation and characterization. Pioneering work by the laboratory of Dr. Yamanaka showed that fibroblasts transduced with retroviral vectors expressing four transcription factors, Oct4, Klf4, Sox2 and cMyc can be reprogrammed to become pluripotent stem cells that appear almost indistinguishable from ESC. In contrast to ESC, iPS cells are genetically identical to the individual from whom they are derived, raising the prospect of utilizing iPS cells for autologous cell based therapies without risk of rejection. We have previously developed a single lentiviral vector expressing a stem cell cassette, named STEMCCA, capable of generating iPS cells from post-natal fibroblasts and peripheral blood with very high efficiency that became the industry standard. We have also modified it to make it excisable and have used it to generate mouse and human iPS cells free of exogenous transgenes. For the last several years we have used iPS cells for disease modeling and study their potential for regenerative medicine.

iPS Cell Modeling of Intestinal Differentiation

One major focus of the lab is the utilization of iPS Cells for the study of intestinal differentiation with a particular interest in infectious diseases as well as Colorectal Carcinoma (CRC). For this purpose we have generated iPSC from individuals suffering from FAP and Lynch Syndrome, the two most highly penetrant hereditary forms of CRC. We have established in the lab robust differentiation protocols for the induction of intestinal specification of these disease-specific iPSC. By studying the earlier events associated with intestinal differentiation comparing the normal and mutant cells we aim at discovering the basic mechanisms involved in tumor development in the gastrointestinal tract. We are also very interested in studying viral infections of the gut. For this purpose we have used our HIO differentiation protocol to study the effect of SARS-CoV-2 in affecting the intestinal epithelium and we are now expanding these studies to compare Ebola virus vs Marburg virus infection of the gut.

FAP-specific iPSC-derived intestinal organoids

FAP-specific iPSC-derived intestinal organoids

iPS Cell Modeling of Hepatic Differentiation

Several projects in the lab utilizes the liver differentiated progeny of iPSC to study genetic and infectious diseases affecting the liver. We have an established collaboration with the Mühlberger lab at the BU NEIDL to study Ebola virus entry and replication utilizing human iPSC-derived hepatocytes. By accessing primary human target cells we hope to establish a new paradigm in the use of iPSC-derived cells for infectious diseases.

iPSC_EBOV_05

Ebola viral inclusions in human iPSC-derived hepatocytes

iPS Cell Modeling of Immune / Inflammatory Cell Differentiation

Our long standing interest in the immune system now focuses in the utilization of iPSC-derived immune cells, including myeloid dendritic cells (mDCs), microglia, T cells and others as the basis to study several inflammatory and infectious diseases such as filovirus infection and HIV. In collaboration with the Gummuluru and Henderson labs we are utilizing iPSC-derived microglia cells to study the role of microglia in HIV latency in the neural system, as well as the role of opiod addiction in affecting HIV infection. Another project in the lab focuses on the generation of T/NK cells and their potential use as modulators of immune tolerance and immunotherapy. We are combining novel engineered stromal cells, notch signaling stimulation and gene editing to explore a way to direct the differentiation of iPSC into hematopoietic progenitors and into a T/NK cell lineage.

iPSC_CJD_PrP

CJD-specific iPSC-derived motor neurons express high levels of PrP protein

iPS Cell Modeling of Neurodegeneration

We have established the largest iPSC library of E200K mutant cells from individuals with Creutzfeldt Jakob Disease. We are utilizing their differentiated motor neurons to study expression of normal vs mutant PrP and the mechanisms behind Prion mediated neural toxicity. We have also created syngeneic CRISPR corrected lines and we are establishing cerebral organoids from normal and mutant cells to study the role of abnormal prion protein in these organoids.

Lab Members

Aldana

Aldana Gojanovich, PhD | Postdoctoral Research Fellow

Aldana was born in a small town called Verónica in the province of Buenos Aires, Argentina. Aldana holds a Biotechnology and Molecular Biology degree from the University of La Plata (UNLP) and a Ph.D. in Biological Sciences from the University of Buenos Aires (UBA). After spending three years in Mendoza (becoming an expert in Malbec) she joined the Mostoslavsky Lab to develop an iPSCs-based model of neurodegenerative diseases using patient-specific iPSC with mutations causing Creutzfeldt-Jakob Disease. Outside the lab Aldana enjoys walking around Boston, good music, good food and watching TV series and movies.

Liz Flores

Elizabeth Yvonne (Liz) Flores | PhD Student
 

Liz is a PhD student in the Mostoslavsky and Mühlberger labs at Boston University. She is originally from California, but has spent most of her life on the East Coast. She graduated with a BS in Biology and an MS in Molecular Biology from Montclair State University. She is broadly interested in the molecular mechanisms underlying infectious diseases and is currently modeling filovirus infections in iPSC-derived human intestinal organoids. Aside from scientific research, Liz loves attending art galleries, playing the piano, traveling and film.

Julian Amirault

Julian Amirault | PhD Student

Julian is a PhD student in the Mostoslavsky lab studying T cell differentiation and the molecular mechanisms governing CD8 vs CD4 lineage specification. Building on our previous studies of the role of Notch signaling in early definitive hematopoietic specification, Julian is exploring the signaling cues that modulate the generation of T cell lymphocytes from human iPSC.

Victor Schingo

Victor Schingo | Undergraduate Student

Victor is currently a Biochemistry major/molecular biology/pre-med student at Boston University. He currently has the tough task of utilizing iPSC containing inducible forms of oncogenes relevant to Colorectal cancer to study the initiation of tumorigenes in the GI tract using iPSC-derived intestinal organoids.

MengWei Yang

MengWei Yang | Lab Manager

MengWei graduated from University of Massachusetts Amherst with a bachelor’s degree in Biology and Chinese. MengWei is the current lab manger for the Mostoslavsky lab. He was born in Fuzhou, China but immigrated to the United States at the age of 7. In his free time he loves being outdoors and fishing. One fun fact about him is that he plays the clarinet.

Alumni

Postdoctoral Fellows

Cesar
Cesar Sommer, PhD
Postdoctoral Fellow
Andreia
Andreia G. Sommer, PhD
Postdoctoral Fellow/Lab Manager
Javi
Francisco Javier Molina Estevez (Javi), PhD
Postdoctoral Fellow
Amalia Capilla Villanueva
Amalia Capilla Villanueva, PhD
Postdoctoral Fellow
Dar
Dar Heinze, MD PhD
Postdoctoral Fellow

Graduate Students

Dolly
Dolly Thomas
PhD Student
Maggie
Maggie Baker
PhD Student
Whitney
Whitney Manhart
PhD Student
Aditya
Aditya Mithal
MD PhD Student
Mona
Mona Haratianfar
MSc Student
Jennifer Wang
Jennifer Wang
MSc Student
Rita
Rita Matos
PhD Student

Undergraduate Students

Rubayath
Rubayath Mohsen
Summer student
Patrick
Patrick Joynt
Undergraduate Student
Monica
Zhe (Monica) Zhong
Undergraduate Student
Arul Malhotra
Arul Malhotra
RISE Program Student, BU

Research Technicians

Ryan
Ryan Mulhern
Research Technician
Sunny
Seonmi "Sunny" Park
Lab Manager
Andrew
Andrew McCracken
Lab Manager

Visiting Scientists

Ana
Ana Lucia Hael, Biochemist
Visiting Scientist from Tucuman, Argentina
Karin
Karin Gustaffson
Visiting PhD Student from Uppsala University, Sweden
Juan
Juan Cruz Casabona, PhD
Visiting Scientist from Leloir Institute, Buenos Aires, Argentina
Wiktoria
Wiktoria Maria Suchorska, PhD
Visiting Scientist from Poznan, Poland
Veronica Furmento
Veronica Furmento, PhD
Visiting Scientist from Escobar, Argentina
Lucia Moro
Lucia Moro, PhD
Visiting Scientist from Escobar, Argentina
Claudia
Claudia Yahalom, MD
Director of Pediatric Ophtalmology at Hadassah Hospital. Visiting Scientist from Jerusalem, Israel
Ivonne
Ivonne Ramirez
GI Research Fellow
Veronica
Veronica Marignac, PhD
Visiting Scientist from Entre Rios, Argentina

Publications

To access Lab Protocols, go to our CReM Site

Heinze et al SCR 2022
Heinze et al, SCR, 2022
Scoon et al SCR 2022
Scoon et al, SCR, 2022
Berical et al NC 2022
Berical et al, Nat Com, 2022
Mithal et al SCR 2021
Mithal et al, SCR, 2021
Akiyama et al J Vir 2020
Akiyama et al, J Vir, 2020
Yuen et al Front Immunol 2021
Yuen et al, Front Immunol, 2021
Dost et al Cell Stem Cell 2020
Dost et al, Cell Stem Cell, 2020
Mithal et al Nat Comm 2020
Mithal et al, Nat Comm, 2020
Hurley et al CSC 2020
Hurley et al, Cell Stem Cell, 2020
Park and Mostoslavsky CPSTB 2018
Park and Mostoslavsky, CPSTB, 2018
Sommer et al, PLoS One 2018
Sommer et al, PLoS One, 2018
  Kitano, Nature Communications, 2017
Kitano et al, Nature Communications, 2017
Zhang, Scientific Reports, 2017
Zhang et al, Scientific Reports, 2017
Park, Stem Cell Reports, 2016
Park et al, Stem Cell Reports, 2016
Schlimgen, American College of Occupational and Environmental Medicine, 2016
Schlimgen et al, American College of Occupational and Environmental Medicine, 2016
Zhou, Nature Communications, 2016
Zhou et al, Nature Communications, 2016
Etchegaray, Nature Cell Biology, 2016
Etchegaray et al, Nature Cell Biology, 2016
Bar-Nur, Nature Biotechnology, 2015
Bar-Nur et al, Nature Biotechnology, 2015
Wilson, Stem Cell Reports, 2015
Wilson et al, Stem Cell Reports, 2015
For a full list of publications check PubMed

Life in the Lab

Citizenship Award Mostoslavsky

Dr. Mostoslavsky receives Outstanding Citizenship Award 2019 DOM BU

Ky CHA Award Mostoslavsky

Dr. Mostoslavsky receives Ky CHA Award in Stem Cell Technologies 2019

CReM Evans Day

CReM Evans Day 2019

Halloween 2019

The Mostoslavsky Lab Halloween 2019

Gustavo Innovator of the Year

Dr. Gustavo Mostoslavsky is BU Innovator of the Year 2017

Read Bostonia article here

Gustavo and lab BBQ

The Mostoslavsky Lab BBQ Spring 2019

outing

Enjoying a "Pepito"

Lab at the Tissue culture

Intense tissue culture day at the Mostoslavsky lab

Left to Right: Gustavo, Sunny, Dar, Amalia and Aditya

Gustavo and lab BBQ

The Mostoslavsky Lab BBQ Summer 2017

Gustavo and Whitney

Poster Presentation

Gustavo and Whitney at Evans Day 2016

Gustavo and Dar

Poster Presentation

Gustavo and Dar at Evans Day 2016

Retreat

CReM Retreat 2016

Retreat

CReM Retreat 2016

Gustavo's Birthday

Gustavo's Birthday

Dr. Murphy, Dr. Kotton and Dr. Mostoslavsky

Co-Directors CReM

Dr. Murphy, Dr. Kotton and Dr. Mostoslavsky
The CReM Musketeers

Halloween Party

Halloween Party

Halloween Party

Halloween Party

Winter BBQ 2017

Winter BBQ 2017

The Argentinian Way

Mostoslavsky Lab

Mostoslavsky Lab

Winter BBQ 2017

BBQ at the CReM

Every year we enjoy a Summer and Winter BBQ together! YES, even with 3 feet of snow!