HUMANOID

We reverse-engineer personalized model systems, i.e., human organoids to study the dysregulated-communication networks that drive diseases. 

Soumita Das, Ph.D.

Faculty Director


THE PROBLEM: Animal models fall far short of being able to predict human responses. Similarly, cultured immortalized cells fail to recapitulate the biology of primary cells.  

THE SOLUTION: Recent developments in 3D culture technology allow embryonic and adult mammalian stem cells to self-organize and form organoids reflecting key structural and functional properties of organs such as kidney, lung, gut, brain, and pancreas. Scientists now appreciate that "dimensionality" and context matter. Organoids are technically the closest in vivo model and are destined to become central to development of new therapeutic strategies and tools for advancement of personalized medicine.

At Humanoidâ„¢ we envision to:

  • Enable studies investigating cell-cell, tissue-tissue, interorgan, and host-microbe communications after accounting for dimensionality and heterogeneity in physiology and disease.
  • Changing the game in modeling human diseases and setting new standards for translational research here at UCSD and in the greater SD area.
  • Engaging the SD community to becoming one of the most versatile 3D organoid core facilities in US.
  • Developing a service and teaching oriented core that offers ready-to-use 3D human model platforms for specific organs and primary cells.
  • Ensuring widespread access to this technology by providing on-site expertise for day-to-day operations.
  • Training the next generation of students and fellows/faculty, providing theoretical and reagent support, and consulting on complex co-culture assays, drug screening, gene editing, etc.
  • Maximizing our impact, outreach and visibility by enabling researchers in both academic institutions (UCSD, Non-UCSD) and industries.

OUR SCOPE: All tissues, either normal or diseased, can be developed into organoids, as long there are adult stem cells, with a few exceptions (list exceptions). Personalized laboratory models (i.e., known phenotype, genotype) will be prepared, on-demand, in a matter of weeks, which will be helpful to screen multiple different drugs on the tumor and help researchers/clinicians to bring precision medicine to individuals with any disease. 

Adult stem cell derived organoids to support the proposed core:

Gastrointestinal Organoids:

Esophagus and Stomach

  • Long-term culturing of human esophageal and stomach organoids that maintain characteristics of the original tissue.
  • Modeling eosinophilic esophagitis, esophageal Ca, Helicobacter pylori infection, gastric cancers, etc.

Small Intestine and Colon

  • Stable, long term culture of small intestinal or colonic organoids described as 'mini gut'.
  • Modeling celiac disease, drug induced colitis, IBS, IBD, colon polyps, cancers, etc.

Liver

  • Long term culture of organoids consisting of progenitor cells expressing early bile duct and hepatocyte markers.
  • Modeling NAFLD/ NASH, PBC, liver cancers, etc.

Pancreas

  • Long term progenitor organoids consisting mostly pancreatic duct cells.
  • Modeling pancreatic ductal adenocarcinomas (PDA).
     

Non-GI Organoids

Mammary gland

  • Long term culture of mammary gland organoids comprising distinct basal and luminal compartments.
  • Modeling pre-neoplastic and neoplastic diseases of the breast

Prostate

  • Long-term stable expansion of primary prostate organoids, composed of differentiated basal and luminal cells that reconstitute prostate glands.
  • Modeling pre-neoplastic and neoplastic diseases of the breast

Lung

  • Short term culture of mouse and human alveolospheres from single type I and type 2 alveolar cells, containing both cell types in the same organoid.
  • Modeling exposure to smoking substances of abuse, cystic fibrosis, lung cancer, etc.

iPSC-derived: [see Image Catalog]

  • Brain (neural stem cells, neurons, astrocytes, oligodendrocytes,)
  • Cardiomyocytes (beating muscle)
  • Retina

 

PROPOSED USES:

  • Organogenesis/Organ development studies
  • Infectious disease: Because organoids represent all cellular components of a given organ, they are well placed for infectious disease studies, particularly for pathogens that are dependent on specialized cell types. Several coculture models involving epithelial- immune or non-immune cells to study host microbe interface.
  • Cancer: Neoplastic, pre-neoplastic, and non-neoplastic organoids provide unique platform for functional testing of drug sensitivity and toxicity. An early 2018 report demonstrated the clinical reality in predicting outcome -"in 100 percent of cases, if a drug didn't work on a patient's organoids, then it didn't work in the patient, and that in nearly 90 percent of cases, if a drug did work on the organoids, then it worked in the patient, too".
  • Personalized medicine: Tumor organoids, like tumor, have irregular and altered kinetics vs. normal tissue derived organoids and demonstrate a heterogeneous genetic make-up. Drug response for an individual patient can be validated using personalized tumor organoids.
  • Future Directions, R&D efforts to maintain leadership in the field:
    • 3D human organ chips
    • Gene editing and biobanking genotyped organoids

How HUMANOIDTM differs from other organoid cores



Example: Modeling the complex host-microbe and cell-cell communication in Inflammatory Bowel Disease (IBD)


A Model and Diagram of Inflammatory Bowel Disease
Figure adapted from a Manuscript in Preparation (Swanson L et al., 2018)