Hematopoietic stem cells (HSC) maintain multi-lineage blood formation throughout our lifetime. Balancing stem cell regeneration and differentiation commitment to produce mature blood cells is quintessential for a healthy hematopoietic system. Dysregulation of such HSC fate determination processes can lead to loss of immune function, bone marrow failure, and malignant transformation during aging. However, up to date very little is known about the molecular events driving age-related HSC changes and how they contribute to disease.
Understanding age-associated molecular alterations will not only uncover fundamental mechanisms guiding function of HSCs, but may also allow for therapeutic intervention to “rejuvenate” aged hematopoietic systems and possibly even prevent age-associated hematopoietic diseases. Our mission is to clarify the central mechanisms establishing and guarding sustained hematopoietic stem cell function, particular those that drive leukemogenesis, if disrupted.
We develop innovative genetic mouse models, use ex vivo and in vivo primary mouse and human stem cell assay systems, exploit lentiviral gene transfer, and apply state-of-the-art molecular biology and next generation sequencing techniques.
Our recent work has uncovered a key role of the amount of readily accessible intracellular iron (termed labile iron pool, LIP) in instructing HSC self-renewal. We are currently investigating the precise molecular mechanism of action, particularly focusing on metabolic and non-enzymatic molecular pathways relying on iron – a completely uncharted territory for healthy as well as leukemic stem cells.
Our past work has demonstrated a causative role of even minimal dosage alterations of a key transcription factor instructing hematopoiesis, PU.1, observed in hematopoietic stem cell aging to myeloid leukemia evolution. Our current efforts focus on understanding how such slight deviations from optimal PU.1 dosage lead to the erosion of PU.1-dependent gene expression programs, and in which way a slightly altered PU.1 gene expression network can functionally cooperate with age-associated inactivation of epigenetic regulators (TET2 and DNMT3A).
Teamed-up with Dr. Ana Maria Cuervo (Dept. of Developmental & Molecular Biology), the discoverer of a highly precise protein degradation pathway named chaperone-mediated autophagy, we are investigating the role of this stress-related molecular defense mechanism in leukemic stem cell evolution and maintenance.
Nationality: German
Official role in lab: Principal Investigator
Unofficial roles in lab: Strategic planner, PR agent and financial officer
Project(s): All and none of them, really (ideas are cheap!!!)
Previous professional training:
University of Kaiserlautern, Germany (M.Sc. in Biology)
Harvard University, Cambridge, MA and University of Freiburg i.Br., Germany (Ph.D. in Hematology)
Albert Einstein College of Medicine, Bronx, NY (Postdoc; Oncology/Stem cell biology)
Why I am doing research: Most stimulating and rewarding way to spend my time doing something I believe in alongside an incredibly inspirational group of team members and colleagues.
Dream lab bench mate: Albert Einstein (what a question?!) – for his unparalleled ingenuity, vision, and humanity.
Motivation in the face of failing experiments: Steak (bloody, and keep the vegetables please!!!) paired with red wine (a lot of it) and a friend to make plans for how to immediately leave research.
Outside the lab: Remotely annoying anyone in the lab.
Nationality: Indian
Official role in lab: Post-Doctoral Research Fellow
Unofficial roles in lab: Photographer
Project(s): Iron homeostasis regulatory pathways in Leukemic Stem Cells
Previous professional training:
University of Calcutta, India, B.Sc. (Honors) Biochemistry
University of Calcutta, India, M.Sc. Biochemistry
University of South Carolina, Columbia, US, Ph.D. Chemistry
Why I am doing research: Trying to make sure my brain gets some regular work out, even if I miss my gym!
On a more serious note, I would love to leave a footprint in this world and research is a tool I chose to help me progress towards that goal.
Dream lab bench mate: Rosalind Franklin – for sheer grit, determination and dedication! Also #WiSci :D
Motivation in the face of failing experiments: Netflix and Chill with chicken!
Outside the lab: Indoors – Being a couch potato with a good book or TV show
Outdoors: Roaming around with my camera
Nationalities: French, Spanish
Official role in lab: Research Technician
Unofficial roles in lab: Stage manager and elf.
Projects: Mouse model set up for Molecular safeguards in MDS.
Previous professional training/experience:
Catholic University of Lyon, France (B.S. in Biology-Biochemistry)
University of Texas at Dallas, Richardson, TX (Research Trainee)
Northwestern University, Chicago, IL (Research Trainee)
French Reference Center on Paraneoplastic Neurological Diseases and Autoimmune Encephalitis, Lyon, France (Laboratory Technician)
Why am I doing research? Because I surely watched too many TV shows as a kid and thought that wearing a lab coat and using words that nobody understands was cool. In reality, I don’t even understand some of those words myself – but getting there! Doing research is exciting and an opportunity to meet a lot of inspirational people - who will, of course, use lots of words that I may not understand (YET!!) but make all of us look as cool as on TV!
Dream lab bench mate: Who said I needed a bench mate? OK, OK - I am pretty sure Sheldon Cooper would understand my sarcasm - or we’d end up killing each other!
Motivation in the face of failing experiment: Protocol: 1) Take the stress out at the gym. 2) Devour tons of chocolate (because I deserve it and chocolate is life!!). 3) Cry because I messed with my meal plan. 4) Repeat steps 1-3 as long as it takes to get that #$%$^&#@ PCR to work.
Outside the lab: Travel & photography, reading, fitness (weight-lifting).
Nationality: Chinese
Official role in lab: Post-doc
Unofficial roles in lab: Mouse whisperer
Project(s): The roles of chaperone mediated autophagy in acute myeloid leukemia.
Previous professional training:
Wuhan University, China (M.Sc. in Basic Medical Science)
Wuhan University, China (Ph.D. in Basic Medical Science)
Why I am doing research: To explore the mysteries in the world
Dream lab bench mate: Hermione Granger
Motivation in the face of failing experiments: Hope for success in the repeat – modify and try it again!!!
Outside the lab: Seeking out delicious food everywhere.
Nationality: Greek
Official role in lab: Ph.D. student
Unofficial roles in lab: Event planner and chef patisseur
Project(s): Moderate dose alterations of key transcription factors driving hematopoietic stem cell transformation during aging.
Previous professional training:
University of Patras, Greece (B.Sc. in Biology)
University of Patras, Greece (M.Sc. in Biotechnology)
Albert Einstein College of Medicine, Yeshiva University, Bronx, NY (M.Sc. in Hematology/Oncology)
Why I am doing research: The opportunity it gives me to formulate new hypotheses and investigate something unknown is fascinating
Dream lab bench mate: Aristotle - Excellence is never an accident. It is always the result of high intention, sincere effort, and intelligent execution; it represents the wise choice of many alternatives - choice, not chance, determines your destiny. Be a free thinker and don't accept everything you hear as truth. Be critical and evaluate what you believe in.
Motivation in the face of failing experiments: The amazing and supportive lab mates and the new "sunny" days that will surely follow!
Outside the lab: Spending time with friends and family, training and fitness, exploring the world
Nationality: Greek
Official role in lab: Research technician.
Unofficial roles in lab: Mouse primary care physician (or pathologist – whatever comes first), guarantor and guardian of day-to-day lab essentials.
Project(s): Bits and pieces on all lab projects.
Why I am doing research: Coming from a very different professional background, I realized that research is motivational, rewarding, and perhaps one of the most significant contributions to society.
Dream lab bench mate: Sherlock Holmes, for his intellect, methodology and weird sense of humor.
Motivation in the face of failing experiments: Coffee (black, no sugar, no milk), and then more coffee (black, no sugar, no milk).
Outside the lab: Gym, Board Games, Cooking, Movies.
Nationality: Taiwanese
Official role in lab: Graduate student & Postdoc
Unofficial roles in lab: Cake messenger
Project(s): The labile iron pool as a rheostat for stem cell function
Previous professional training: Emory University, Atlanta, GA (BS in Neuroscience & Behavioral Biology)
University of Pennsylvania, Philadelphia, PA (MS in Biotechnology)
Albert Einstein College of Medicine, Bronx, NY (PhD in Biomedical Sciences)
Why I am doing research: I find the process of assigning values to ideas particularly stimulating and empowering.
Dream lab bench mate: James Bond - for his audacity, intelligence and assertion.
Motivation in the face of failing experiments: To feel the adrenaline of fearlessness on a racetrack.
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Nationality: Indian
Official role in lab: Research Associate
Unofficial roles in lab: Captain of a tightly run ship
Project(s): CSC-PDL collaboration projects, tissue banking and xenocore.
Previous professional training:
Pondicherry University, Pondicherry, India (B.Pharm)
Rajiv Gandhi University of Health Sciences, Bangalore, India (M.Pharm in Pharmacology)
Syngene Intl. Ltd., Bangalore, India (Junior Manager-Quality Control)
Anthem Biosciences, Bangalore, India (Senior Scientist-Quality Control)
Albert Einstein College of Medicine, Bronx, NY (Research Technician)
Why I am doing research: In search of remedies-serving mankind.
Dream lab bench mate: Definitely my boss- for her untiring, smart and hard work (the person I witnessed by my eyes)
Motivation in the face of failing experiments: Failures happen everywhere, but most problems have a solution (“this is not the end of the world”- my boss).
Outside the lab: Family and church
Nationality: Indian
Official role in the lab: Research Trainee
Project(s): Various CSC-PDL collaboration projects
Previous professional training:
Pharmacy Undergraduate: Sri Padmavathi Mahila university, Tirupathi, India
Pharmacology Graduate: Long Island University, Brooklyn, New York
Volunteer pharmacy technician: 8th Ave pharmacy, New York
Volunteer research trainee: Mount Sinai
Why I am doing research: It’s a big secret
Dream lab bench mate: Too early to say
Motivation in the face of failing experiments: Let the experiment understand how conscious and restraint I am
Outside the lab: Partying, Learning new things like violin and Garba for this year.
CORE TEAM:
Mariana Ferreira, M.Sc. - Research Technician (2015-2018), now research technician at MSKCC
Margarida Teixeira, Ph.D. - Postdoctoral Research Fellow (2016-2018), now Research Applications Scientist with Beckton Dickinson, NY, NY
Lumie Benard, M.Sc. - Research Technician CSC-PD (2015-2019), now Research Technician at Stelexis Pharmaceuticals, Bronx, NY
Sally Cole, B.Sc. - Research Technician CSC-PD (2016-2018), now Ph.D. student at Columbia University, NY, NY
Stephen Ruiz, B.Sc. - Research Technician and Web Master (2017-2019), now Ph.D. student at Weill Cornell Medical Center, NY, NY
Ujunwa C. Okoye-Okafor, Ph.D. - Postdoctoral Fellow and Research Associate (2018-2021), now Senior Research Associate at Hackensack Meridian Health
VISITING TRAINEES:
November 2019
October 2019
October 2019
September 2019
Lab Summer Party!!!
Group pic!
Waiting for the food
Grillmaster Victor
Grillin’
Rajni (Steidl Lab), Madhuri, Maria and visiting students from Columbia University celebrate in the Holi gathering!
Madhuri, Victor and Yuhong celebrate Holi!
The Will lab and CSCPD unit join together to perform one of the biggest mice sac of the year!
The Will lab and CSCPD unit join together to perform one of the biggest mice sac of the year!
The Will lab and CSCPD unit join together to perform one of the biggest mice sac of the year!
End of the year dinner with the lab!
End of the year dinner with the lab!
HAPPY BIRTHDAY MADHURI!
Surprising Britta with a baby shower!
Yuhong, Cynthia, Maria, and Christine attended the NYSCF Conference held at The Rockefeller University in New York City which ran from October 23 to October 24.
CONGRATULATIONS DR. CHRISTINE KAO ON YOUR AMAZING THESIS DEFENSE!
HAPPY BIRTHDAY MARIA!
From left: Britta, Cynthia, Uli, Dan, Laura
Maria and Britta @ “Gene Regulation in Differentiation and Cancer”
December 4th, 2019, Boston, USA
We are officially a safe lab :) !!!
Many thanks to my phenomenal team for their respectful, safe, and hard work they put in every day and to the Einstein and Montefiore leadership for this wonderful award.
December 2019
Pandemic mitigation 2020
ISEH 2020
ASH 2020
CONGRATULATIONS, Maria !
FASEB - The Hematologic Malignancies Meeting 2021
We will miss you !!
Good luck !
Chaperone-mediated autophagy sustains hematopoietic stem-cell function
Spearheaded by Dr. Shuxian Dong and in collaboration with Dr. Ana Maria Cuervo, we studied the role of chaperone-mediated autophagy (CMA), a selective form of lysosomal protein degradation, in sustaining HSC function in adult mice. We found that CMA is required for protein quality control in stem cells and for the upregulation of fatty acid metabolism upon HSC activation. We uncovered that CMA activity decreases in HSC with age and show that genetic or pharmacological activation of CMA can restore the functionality of old mouse and human HSCs. Together, our findings provide mechanistic insights into a role for CMA in sustaining quality control, appropriate energetics and overall long-term HSC function. Our work suggests that CMA may be a promising therapeutic target for enhancing HSC function in conditions such as ageing or stem-cell transplantation. (Dong et al., Nature 2021)
Comment by Drs. Nick van Gastel and David T. Scadden in Cell Research
Thrombopoietin receptor–independent stimulation of hematopoietic stem cells by eltrombopag
In this new study, we characterized the mechansim of action of eltrombopag on stimulating hematopoietic stem cell function and uncovered a key role of the amount of readily accessible intracellular iron in instructing hematopoietic stem cell self-renewal (Kao et al., STM 2018).
Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia
Hematopoietic stem cell aging is associated with wide-ranging gene expression alterations. Here we demonstrated that even minimal dose alterations of a key hematopoietic transcription factor, PU.1, predisposes stem cells to malignant transformation (Will et al., Nat. Med. 2015).
Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment
Here, we identified the transcription factor and chromatin remodeler Satb1 as a critical regulator of HSC fate, and provide insight into how hematopoietic stem cells coordinate the regulation of opposing cellular mechanisms such as self-renewal and differentiation commitment upon cell division (Will et al., Nat Immunol 2013).
Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations
Myelodysplastic syndrome (MDS) is an ageing-associated hematologic malignancy, largely lacking curative therapies. In this study we demonstrated that patient-derived aberrant stem and progenitor cells contain epigenetic and genetic alterations which may be exploited for therapeutic targeting (Will et al., Blood 2012).
Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome
Thrombocytopenia is a frequent symptom and clinical challenge in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Eltrombopag is a small molecule thrombopoietin receptor agonist that might be a new option to treat thrombocytopenia in these diseases, provided that it does not stimulate malignant hematopoiesis. In this work, we provide a preclinical rationale for further testing of Eltrombopag for treatment of thrombocytopenia in AML and MDS (Will et al., Blood 2010).
FULL LIST OF PUBLICATIONS
We are always looking for passionate scientists at all experience levels to join our team. If you are interested in working with us, please send your application package consisting of your current resume or CV including the contact information of at least two recent professional references and a cover letter briefly describing your background and your motivation.
Britta Will, Ph.D. Telephone Office : +1 (718) 430-3786
Albert Einstein College of Medicine Main Lab : +1 (718) 430-6430 or 6461
Department of Cell Biology
Chanin Building for Cancer Research Rooms 401/401A and 302B
1300 Morris Park Avenue
Bronx, NY 10461
USA