University of Exeter Medical School

Dr Chloe Rackham

Dr Chloe Rackham

Lecturer in Diabetes

 C.Rackham@exeter.ac.uk

 RILD Building 

 

University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK

Overview

Dr Chloe Rackham graduated with a BSc (Hons) in Human Sciences from King’s College London (KCL), before completing her PhD with Dr Aileen King and Prof Peter Jones, KCL. Doctoral studies focused on strategies to improve the outcomes of islet transplantation, as a therapy for type 1 diabetes (T1D). During her PhD, Chloe was awarded the Nick Hales Young Investigator Award by Diabetes UK as recognition of her work focused on using Mesenchymal Stromal Cells (MSCs) to improve islet transplantation outcomes.

Dr Rackham was awarded the Diabetes Research and Wellness Foundation Professor David Matthews Fellowship in 2018. This research focuses on defining the mechanisms through which MSCs and their “secretome” can be used therapeutically to improve islet graft function and survival. Dr Rackham aims to define MSC-derived secretory products which mimic the therapeutic effects of MSCs to improve donor islet function and host immune responses to transplanted islets.

Dr Rackham has 17 years’ experience (2023) in the field of diabetes and islet transplantation, with a diverse range of experimental techniques applicable to studying islet/beta cell function and survival in vitro and in vivo. Dr Rackham is passionate within her mentorship of students and committed to ensuring a broad knowledge and skills set, within a supportive environment. Dr Rackham is a dedicated researcher with the long term goal of ensuring that beta cell replacement therapies can be offered to the greatest possible number of individuals living with diabetes.

Qualifications

2008 - 2012: PhD in Physiology entitled, “Strategies for improving islet transplantation outcome.” Division of Diabetes and Nutritional Sciences, King’s College London.

2003 - 2006: BSc (Hons) Human Sciences (First Class). King’s College London.

2022 - 2023: Felowship of the Higher Education Academy

Research group links

Back to top

Research

Research interests

Improving islet transplantation outcomes using Mesenchymal Stromal Cells (MSCs)

Allogeneic islet transplantation offers the possibility to treat selected patients with Type 1 Diabetes (T1D). However, limited availability of donor human islet material limits the widespread application of this therapy. Furthermore, the shortage of donor islets is exacerbated by the extensive loss of valuable islet material during pre-transplant culture and during the post-transplantation period. Dr Rackham is interested in a group of adult stem cells called Mesenchymal Stromal Cells (MSCs), as they have multiple roles to enhance islet graft function and survival. Investigating the mechanisms through which MSCs influence donor islet and host immune cells is a key area of Dr Rackham’s research interest. Dr Rackham is interested in harnessing the therapeutic potential of MSCs to improve the efficiency of clinical islet transplantation, so that it can be offered as a therapeutic option to the greatest possible number of individuals living with T1D. 

Harnessing the MSC secretome to improve islet transplantation outcomes

The beneficial effects of MSCs can be largely attributed to soluble MSC-derived trophic factors that influence host immune cells to dampen down adverse immune responses. Preculturing islets with MSC-derived soluble mediators can directly affect islet cells to improve their functional quality in vitro, prior to transplantation. Dr Rackham’s research is focused on defining a “cocktail” of MSC-derived secretory products that can be used to recapitulate the beneficial effects of MSCs in transplantation protocols, and to better understand the mechanisms through which MSCs improve islet function and survival.

Optimizing islet beta cell function through MSC-mediated mitochondrial transfer

It is well established that the generation of ATP and other metabolic coupling factors by mitochondrial metabolism is essential for nutrient-induced insulin secretion, and that impaired mitochondrial function, and thus reduced OCR, results in defective insulin secretion and reduced β-cell survival. Dr Rackham is interested in the mechanisms through which MSCs improve islet mitochondrial bioenergetics and islet insulin secretory function, with her recent studies identifying MSC-mediated mitochondrial transfer as a key mechanism.

Exploring an islet-protective role for native pancreatic mesenchymal stromal cells in health and in type 1 diabetes

Chloe Rackham is interested in determining the role of native pancreatic MSCs in health and in T1D, with a focus on their immunomodulatory islet-protective functions. These studies will enhance our understanding of disease endotypes and will reveal which individuals (or groups of people) are most likely to benefit from MSC-based therapeutic interventions to delay disease progression.

ORCID Profile: https://orcid.org/0000-0003-4314-6109

External Engagement and Impact 

- Diabetes Research and Wellness Foundation – World Diabetes Day talk and discussion, virtual event, 2020

- United Through Diabetes Research Filming, Diabetes Research and Wellness Foundation, London, 100 years of Diabetes Research, Past Present and Future, participation on expert panel, 2021, https://www.drwf.org.uk/news-and-events/news/drwf-events-united-through-diabetes-virtual-event/ 

- JDRF Lab Visit: The patron’s club day - theme Type 1 diabetes - the journey and Exeter's strategies to help, 14th November 2022, Presentation of research, titled “MSCs as a strategy to protect beta cells” and discussion 

- Diabetes UK – Inside the lab – preparation of website article about Diabetes UK-funded studentship, 2023 (https://www.diabetes.org.uk/about_us/news/inside-lab-shape-shifting-cells-and-beta-cell-transplants), 

- Diabetes UK/JDRF Steven Morgan Foundation Lab tour and Discussion, March 2023

- JDRF Accelerator Programme CEO Evening Reception, 14th June 2023, Oxford and Cambridge Club, London

-May 2023 – Pint of Science, Diabetes UK sponsored event, “Diabetes, blood, sweat and new frontiers”, talk entitled “Shape-shifting Stem Cells – hope on the horizon to treat and prevent type 1 diabetes” https://pintofscience.co.uk/event/diabetes-blood-sweat-and-new-frontiers 

Research projects

  • Improving islet transplantation outcomes by harnessing the mesenchymal stromal cell (MSC) secretome to target the donor islet graft
  • Harnessing the MSC secretome to target host immune cells, to reduce innate inflammatory reactions and adaptive T cell responses to the islet graft
  • Optimizing beta cell function through MSC-mediated mitochondrial transfer
  • Exploring an islet-protective role for native pancreatic mesenchymal stromal cells in health and in type 1 diabetes

Grants/Funding

2019-2022: Diabetes Research and Wellness Foundation Professor David Matthews Non-Clinical Research Fellowship awarded to Dr Chloe Rackham, “Improving islet transplantation outcomes by harnessing the mesenchymal stromal secretome to target the donor islet graft and host environment”, £194, 934

2017-2018: Society for Endocrinology, Early Career Grant awarded to Dr Chloe Rackham, “Mitochondrial transfer from Mesenchymal Stromal Cells to islets as a novel mechanism to enhance insulin secretory function”, £10,000

2019-2021: King’s Health Partners Research and Develop fund, “Using Mesenchymal Stem Cell secretory products to improve the outcomes of human islet transplantation”. Role Co-I, PI Prof Peter Jones, King’s College London (KCL), Co-Is Dr Aileen King and Dr Pratik Choudhary (KCL), £78, 999

2016-2019: Diabetes UK project grant, “Using the MSC secretome to improve the outcomes of islet transplantation”, awarded to Prof Peter Jones and Dr Chloe Rackham, £237,642.

Research grants

  • 2022 Diabetes UK
    Diabetes UK funded PhD studentship (Principal Investigator/Primary Supervisor), £97,869, “Harnessing the capacity of MSCs to rescue islet cells from the inflammatory demise after transplantation and during the pathogenesis of diabetes”
  • 2022 Juvenile Diabetes Research Foundation
    JDRF Strategic Research Agreement (SRA) - Project Concepts FY23 awarded to Chloe Rackham (Principal Investigator), Sarah Richardson and Noel Morgan, 375,000 USD, Exploring an islet-protective role for native pancreatic mesenchymal stromal cells in health and in type 1 diabetes
  • 2021 Medical Research Council
    Medical Research Council project grant awarded to Peter Jones, Chloe Rackham (Co-Investigator) and Aileen King, £351,315, “Improving beta cell function by mesenchymal stromal cells: novel mechanisms and cell-free translational potential

Back to top

Publications

Journal articles

Gribben C, Lambert C, Messal HA, Hubber E-L, Rackham C, Evans I, Heimberg H, Jones P, Sancho R, Behrens A, et al (2023). Ductal Ngn3-expressing progenitors contribute to adult β cell neogenesis in the pancreas. Cell Stem Cell, 30(4), 498-499.  Author URL.
Hong T-W, Caxaria S, Daniels Gatward LF, Hussain S, Zhao M, King AJF, Rackham CL, Jones PM (2023). Mesenchymal stromal cell secretory molecules improve the functional survival of human islets. Diabet Med, 40(12). Abstract.  Author URL.
Gribben C, Lambert C, Messal HA, Hubber E-L, Rackham C, Evans I, Heimberg H, Jones P, Sancho R, Behrens A, et al (2021). Ductal Ngn3-expressing progenitors contribute to adult β cell neogenesis in the pancreas. Cell Stem Cell, 28(11), 2000-2008.e4. Abstract.  Author URL.
Hubber EL, Rackham CL, Jones PM (2021). Protecting islet functional viability using mesenchymal stromal cells. Stem Cells Transl Med, 10(5), 674-680. Abstract.  Author URL.
Rackham CL, Hubber EL, Czajka A, Malik AN, King AJF, Jones PM (2020). Optimizing beta cell function through mesenchymal stromal cell-mediated mitochondria transfer. STEM CELLS, 38(4), 574-584.  Author URL.
Arzouni AA, Vargas-Seymour A, Dhadda PK, Rackham CL, Huang G-C, Choudhary P, King AJF, Jones PM (2019). Characterization of the Effects of Mesenchymal Stromal Cells on Mouse and Human Islet Function. STEM CELLS TRANSLATIONAL MEDICINE, 8(9), 935-944.  Author URL.
Hubber E, Rackham C, Pullen T, Jones P (2019). Investigating mesenchymal stromal cell mediated support of islets after exposure to transplantation related stressors. Endocrine Abstracts
Rackham CL, Dhadda PK, Simpson SJS, Godazgar M, King AJF, Jones PM (2018). Composite mesenchymal stromal cell islets: Implications for transplantation via the clinically preferred intraportal route. Transplantation Direct, 4(4).
Rackham CL, Amisten S, Persaud SJ, King AJF, Jones PM (2018). Mesenchymal stromal cell secretory factors induce sustained improvements in islet function pre- and post-transplantation. CYTOTHERAPY, 20(12), 1427-1436.  Author URL.
Rackham CL, Jones PM (2018). Potential of mesenchymal stromal cells for improving islet transplantation outcomes. CURRENT OPINION IN PHARMACOLOGY, 43, 34-39.  Author URL.
Arzouni AA, Vargas-Seymour A, Rackham CL, Dhadda P, Huang G-C, Choudhary P, Nardi N, King AJF, Jones PM (2017). Mesenchymal stromal cells improve human islet function through released products and extracellular matrix. CLINICAL SCIENCE, 131(23), 2835-2845.  Author URL.
Rackham CL, Vargas AE, Hawkes RG, Amisten S, Persaud SJ, Austin ALF, King AJF, Jones PM (2016). Annexin A1 is a Key Modulator of Mesenchymal Stromal Cell-Mediated Improvements in Islet Function. DIABETES, 65(1), 129-139.  Author URL.
Moreau A, Blair PA, Chai J-G, Ratnasothy K, Stolarczyk E, Alhabbab R, Rackham CL, Jones PM, Smyth L, Elgueta R, et al (2015). Transitional-2 B cells acquire regulatory function during tolerance induction and contribute to allograft survival. EUROPEAN JOURNAL OF IMMUNOLOGY, 45(3), 843-853.  Author URL.
Rackham CL, Dhadda PK, Le Lay AM, King AJF, Jones PM (2014). Preculturing Islets with Adipose-Derived Mesenchymal Stromal Cells is an Effective Strategy for Improving Transplantation Efficiency at the Clinically Preferred Intraportal Site. Cell Med, 7(1), 37-47. Abstract.  Author URL.
Rackham CL, Jones PM, King AJF (2013). Maintenance of Islet Morphology is Beneficial for Transplantation Outcome in Diabetic Mice. PLOS ONE, 8(2).  Author URL.
Rackham CL, Dhadda PK, Chagastelles PC, Simpson SJS, Dattani AA, Bowe JE, Jones PM, King AJF (2013). Pre-culturing islets with mesenchymal stromal cells using a direct contact configuration is beneficial for transplantation outcome in diabetic mice. CYTOTHERAPY, 15(4), 449-459.  Author URL.
Mucha N, Clarkin C, Rackham C, King A, Wheeler-Jones C, Jones P (2011). A potential role for EphB:Ephrin B expression in the regulation of beta cell and islet endothelial cell communication. Diabetologie und Stoffwechsel, 6(04).
Rackham CL, Chagastelles PC, Nardi NB, Hauge-Evans AC, Jones PM, King AJF (2011). Co-transplantation of mesenchymal stem cells maintains islet organisation and morphology in mice. DIABETOLOGIA, 54(5), 1127-1135.  Author URL.
Skowera A, Ellis RJ, Varela-Calvino R, Arif S, Huang GC, Van-Krinks C, Zaremba A, Rackham C, Allen JS, Tree TIM, et al (2009). CTLs are targeted to kill β cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope (vol 118, pg 3390, 2008). JOURNAL OF CLINICAL INVESTIGATION, 119(9), 2843-2843.  Author URL.
Skowera A, Ellis RJ, Varela-Calviño R, Arif S, Huang GC, Van-Krinks C, Zaremba A, Rackham C, Allen JS, Tree TIM, et al (2009). Inherited human cPLA2α deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction. Journal of Clinical Investigation, 119(9), 2844-2844.
Allen JS, Pang K, Skowera A, Ellis R, Rackham C, Lozanoska-Ochser B, Tree T, Leslie RDG, Tremble JM, Dayan CM, et al (2009). Plasmacytoid Dendritic Cells Are Proportionally Expanded at Diagnosis of Type 1 Diabetes and Enhance Islet Autoantigen Presentation to T-Cells Through Immune Complex Capture. DIABETES, 58(1), 138-145.  Author URL.
Skowera A, Ellis RJ, Varela-Calvino R, Arif S, Huang GC, Van-Krinks C, Zaremba A, Rackham C, Allen JS, Tree TIM, et al (2008). CTLs are targeted to kill β cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope. JOURNAL OF CLINICAL INVESTIGATION, 118(10), 3390-3402.  Author URL.

Chapters

King AJF, Rackham CL (2020). Assessing islet transplantation outcome in mice. In  (Ed) Methods in Molecular Biology, 265-280. Abstract.
King A, Rackham C (2013). Co-transplantation of islets with mesenychymal stem cells improves islet revascularization and reversal of hyperglycemia. In  (Ed) Stem Cells and Cancer Stem Cells, Volume 10: Therapeutic Applications in Disease and Injury, 271-282. Abstract.

Conferences

Hubber EL, Rackham C, Pullen TJ, Jones PM (2020). Mesenchymal stromal cell induced gene expression changes in pancreatic islets.  Author URL.
Rackham CL, Hubber EL, Malik AN, Choudhary P, King AJF, Jones PM (2019). Optimising islet transplantation efficiency through mesenchymal stromal cell mediated mitochondrial transfer.  Author URL.
Rackham C, Hubber E, Czajka A, Malik A, Choudhary P, King A, Jones P (2019). Optimising transplantation efficiency through mesenchymal stromal cell modulated improvements in islet mitochondrial bioenergetics.  Author URL.
Rackham CL, Amisten S, Persaud SJ, King AJF, Jones PM (2018). Harnessing the mesenchymal stromal cell secretome to improve the efficiency of islet transplantation.  Author URL.
Vargas AE, Arzouni AA, Dhadda PK, Huang GC, Choudhary P, King AJF, Rackham CL, Jones PM (2017). Beneficial effects of human mesenchymal stromal cells on human islet function via annexin A1 secretion.  Author URL.
Malik AN, Czajka A, Thubron EB, Rackham CL, Austin ALF, King A (2017). Diabetes induced changes in circulating and kidney mitochondrial DNA: a potential novel pathway of renal damage.  Author URL.
Rackham C, Czajka A, Malik A, Huthoff H, King A, Jones P (2017). Mitochondria to the rescue: a novel Mesenchymal Stromal Cell-mediated mechanism of enhanced islet function.  Author URL.
Rackham CL, Dhadda PK, Hawkes RG, Amisten SB, Persaud SJ, Liu B, King AJF, Jones PM (2015). Mesenchymal stromal cells improve islet insulin secretory function via annexin A1 production.  Author URL.
Rackham CL, Dhadda PK, King AJF, Jones PM (2014). Pre-culturing islets with adipose-derived mesenchymal stem cells represents an effective strategy for improving transplantation efficiency at the clinically preferred intraportal site.  Author URL.
Dhadda PK, Rackham C, Le Lay A, Kerby A, Huang GC, Jones P (2014). The effects of three human mesenchymal stromal cell populations upon human islet function <i>in vitro</i>.  Author URL.
Rackham CL, Jones PM, King AJ (2013). Maintaining islet morphology is beneficial for transplantation outcome in diabetic mice.  Author URL.
Dhadda P, Rackham C, Le Lay A, Kerby A, Huang G-C, Jones P (2013). Preculture of Human Islets with Mesenchymal Stem Cells in a Direct Contact Configuration Enhances Islet Function in Vitro.  Author URL.
Rackham C, Dhadda P, Le Lay A, Kerby A, Jones P, King A (2013). Strategies to Improve Intraportal Islet Transplantation Outcome in Mice Using Mesenchymal Stem Cells.  Author URL.
Kerby A, Rackham CL, Chagastelles PC, King AJF (2012). Co-Encapsulation of Islets with Mesenchymal Stem Cells Improves Islet Function.  Author URL.
Dhadda PK, Rackham CL, Simpson SJS, Jones PM (2012). Co-culture of islets with mesenchymal stem cells in direct contact configurations improves islet function in vitro.  Author URL.
Rackham CL, Dhadda PK, Datttani AA, Bowe JE, Jones PM, King AJF (2012). Preculture of islets with mesenchymal stem cells enhances islet function in vitro and produces superior transplantation outcome in diabetic mice.  Author URL.
King AJF, Rackham C, Chagastelles P, Jones PM (2010). Co-transplantation with mesenchymal stem cells improves islet transplantation outcome in mice.  Author URL.

Back to top

Supervision / Group

Postdoctoral researchers

  • Rebecca Dewhurst-Trigg
  • Katie Partridge

Postgraduate researchers

  • Joss Atkins

Back to top

Edit Profile