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Mick Bhatia

Mick Bhatia

Director and Senior Scientist

Tier 1 Canada Research Chair in Human Stem Cell Biology

Michael G. DeGroote Chair in Stem Cell and Cancer Biology

Contact Information

Location: MDCL 5020
Email: mbhatia@mcmaster.ca

Summary

 About the Bhatia Research Program. 

  1. Human Stem Cell Fate Decisions
  2. Disease Focus and Translational Impact
  3. Model Systems and Technologies

 

1. Human Stem Cell Fate Decisions

The Bhatia Research Program focuses on understanding how decisions are made in human adult (somatic) and pluripotent stem cells. These cellular decisions include changing of cell type A to cell type B (differentiation or reprogramming), initiation of cell death (apoptosis), or transformation to a cancerous state. We consider all of these changes as CELL FATE decisions. How this works and how this is governed for individual stem cells forms the core question of our research. 

More recently, our program studies influences on cell fate decisions not only at the level of the cell itself (cell autonomous), but also at the level of the local cellular environment (non-cell autonomous). We now have several projects that compare normal and cancerous stem cells at the cellular and molecular level towards gaining insight into the process of “cancer transformation”.

To assure success, the Bhatia Research Program collaborates with colleagues, and recruits and develops trainees from all sectors and backgrounds who share similar research aspirations and goals of understanding human stem cell fate decisions and applying this knowledge to medical practice to impact patients. In this way, we maintain a fresh and innovative approach that continually adopts alterative perspectives from other fields, and novel tools necessary for progressing our research agenda effectively and rapidly, while maintaining the highest international peer reviewed standards. 

 

2. Disease Focus and Translational Impact

There is a new number one enemy in Canada and it is cancer. Based on 2017 statistics, 1 in 4 Canadians will be diagnosed with cancer, and of these, 1 in 2 individuals will fail to respond to treatment and succumb to the disease. Although survival time for patients has grown longer over the years, showing a direct correlation to the benefits and impact of research, the success rates remain unacceptably low. The recent 2017 statistics hint that current therapies can be improved, and in doing so we would no longer measure survival times but rather measure cure rates instead. 

The Bhatia Program’s disease focus is on HUMAN cancer, and our gateway disease is acute myeloid leukemia (AML), however, much of our research is applicable for other cancers with related mutated signaling pathways and defects, such as breast cancer, colon cancer, and certain types of brain tumors where the findings from our AML studies are expanded and tested. These cancers have been characterised as having cancerous stem cells at the root of the disease and our research comparing normal with cancerous stem cells have provided key insights into new therapeutic approaches we hope to move toward patients.

Our research utilises patient-donated samples allowing us to perform pre-clinical testing using candidate drugs and compare our results against clinical observations. The candidate drugs my program tests are potential therapeutic options to current chemotherapies with the ability to preserve healthy cells while only affecting cancer cells. Traditional chemotherapies are not selective and therefore impact both healthy and cancerous cells alike. Our program identifies new target proteins and pathways found only in cancer cells, using candidate drugs that have little effect on the healthy cells of patients but effectively abolish cancer cells. 

As a result of my programs research findings over the past few years, we are placing greater emphasis on translational research leading towards clinical studies with the goal of positively impacting human health by testing new ideas and therapeutics for patients whose options are currently limited with standard care. To this end, there are numerous ongoing pre-clinical and clinical activities underway towards the goal of Phase I trials.

 

3. Model Systems and Technologies

Human somatic (such as blood stem cells) and pluripotent stem cells (such as embryonic stem cell lines) share common distinct pathways. In studying both, we have gained deeper insights. Similarly, cancerous adult stem cells and cancerous pluripotent stem cells share many properties that are distinct from other cancer cells that make up a tumour. Uniquely, our approach is to study both adult and pluripotent cells in their normal and cancerous states. This allows us to ask scientific questions and explore novel therapeutic approaches that are unique to our program and expertise. Most recently, to unlock the complex heterogeneous system of healthy tissue and cancerous tumour, we are using and developing novel approaches of multi-cytomics (single cell RNAseq, flow and image-based cytometry, clonal tracking).

Our research focuses currently on tissue restricted bone marrow blood stem cells and previously on embryonic stem cell lines. As research in this area has advanced worldwide, so have our options and we now use “induced pluripotent stem cells”. These cells are obtained using Nobel Prize winning “cell reprogramming” technology to reverse cell fate decisions in adult cells. We have further developed an approach to identify and characterise pluripotent cell lines at the earliest stages of cell fate transformation to cancerous states, which has been an instrumental tool for our program in unlocking new candidate therapies.

Our human cancer stem cell and pluripotent stem cell screening platform represents an important and proprietary component of our program being developed over the last decade. This platform focuses on identifying anti-cancer “hits” for cancers using AML as the gateway disease, which is being extended to include breast, colon and brain tumours, and accesses novel chemical space for these ongoing studies. 

We have revealed the influences on cancer stem cells from the microenvironment or “niche” in patients, and we have created a suite of tools from human assays to high content screens for chemical genomics and lead target/drug discovery, which we have moved into Phase I trials. This suite of tools forms the basis of our model systems and platform technologies, and engine of our research program.

 

 

Lab Team

Picture Name Designation Focus Email More Info
Mohammed Almakadi Mohammed Almakadi Graduate Student
Lili Aslostovar Lili Aslostovar Post-Doctoral Fellow
Allison Boyd Allison Boyd Post-Doctoral Fellow
Kapil Dev Chauhan Kapil Dev Chauhan Technical Staff
Tony Collins Tony Collins Research Associate
Juan Luis Garcia-Rodriguez Juan Luis Garcia-Rodriguez Post-Doctoral Fellow
Diana Golubeva Diana Golubeva Graduate Student
Yeonjoon Kim Yeonjoon Kim Graduate Student
Gena Markous Gena Markous Graduate Student
Mio Nakanishi Mio Nakanishi Post-Doctoral Fellow
Luca Orlando Luca Orlando Post-Doctoral Fellow
Deanna Porras Deanna Porras Graduate Student
Jennifer Reid Jennifer Reid Graduate Student
Jennifer Russell Jennifer Russell Technical Staff
Kinga Vojnits Kinga Vojnits Post-Doctoral Fellow
Dimetri Xenocostas Dimetri Xenocostas Graduate Student
Xueli Zhao Xueli Zhao Graduate Student

Selected Publications

Identification of chemotherapy-induced Leukemic Regenerating Cells reveals a transient vulnerability of human AML recurrence

Allison Boyd*, Lili Aslostovar*, Jennifer Reid, Wendy Ye, Borko Tanasijevic, Deanna Porras, Zoya Shapovalova, Mohammed Almakadi, Ronan Foley, Brian Leber, Anargyros Xenocostas, Mickie Bhatia *indicates co-lead authors

Cancer Cell 2018 Sep 10; 34(3):483-498

This research "takes us to another level of being able to understand leukemia". . . and "opens up the door for us to consider new therapies." - Dr. Ronan Foley

Acute myeloid leukemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche

Boyd AL, Reid JC, Salci KR, Aslostovar L, Benoit YD, Shapovalova Z, Nakanishi M, Porras DP, Almakadi M, Campbell CJV, Jackson MF, Ross CA, Foley R, Leber B, Allan DS, Sabloff M, Xenocostas A, Collins TJ, & Bhatia M

Nature Cell Biology. 2017 Nov; 19(11):1336-1347.

Single transcription factor conversion of human blood fate to NPCs with CNS and PNS developmental capacity.

Lee JH, Mitchell RR, McNicol JD, Shapovalova Z, Laronde S, Tanasijevic B, Milsom C, Casado F, Fiebig-Comyn A, Collins TJ, Singh KK, and Bhatia M.

Cell Reports. 2015 Jun 9; 11(9): 1367-76.

“These results enable an understanding of the response of cells to different drugs and different stimulation responses, and allow us to provide individualized or personalized medical therapy for patients suffering with neuropathic pain.” - Dr. Akbar Panju.

Regional localization within the bone marrow influences the functional capacity of human HSCs.

Guezguez B, Campbell CJ, Boyd AL, Karanu F, Casado FL, Di Cresce C, Collins TJ, Shapovalova Z, Xenocostas A, Bhatia M.

Cell Stem Cell. 2013 Aug 1; 13(2):175-89.

"Scientists at Hamilton’s McMaster University have discovered that stem cells located in bone marrow at the ends of bones are superior at regenerating blood cells, including immune system cells, than those found in the shafts of bones." - The Canadian Press

Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells.

Sachlos E, Risueño R, Laronde S, Shapovalova Z, Lee JH, Russell J, Malig M, McNicol JD, Fiebig-Comyn A, Graham M, Levadoux-Martin M, Lee JB, Giacomelli AO, Hassell JA, Fischer- Russell D, Trus MR, Foley R, Leber B, Xenocostas A, Browne ED, Collins T, Bhatia M.

Cell. 2012 June 8; 149(6):1284-97.

"Dr Mick Bhatia, an international leader in cancer stem cell research, discovered that the drug thioridazine, currently used as an antipsychotic, successfully kills the cancer stem cells responsible for initiating leukemias without harming normal stem cells." – Canadian Cancer Society

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