Senotherapeutics Report

The total market value of diseases that could be addressed with (eventual) senotherapeutic therapies totals over $127B.

A new SRF-sponsored report from Longevity.Technology’s Market Intelligence Unit assesses the investment potential of the emerging senotherapeutics sector, examines the potential of targeting cell senescence to treat many major diseases, and deep-dives into key companies working in the field, including:

Atropos Therapeutics; Cleara Biotechnology; Insilico Medicine; Oisin Biotechnologies; Rockfish Bio; Rubedo Life Sciences; and TAmiRNA.

The report identifies the opportunities for growth in the senotherapeutics market and the factors that will drive that growth, together with the challenges that this early market will encounter as it moves into scale and validation.

Who is this report for?

  1. Investors seeking clarity on investment opportunities, market dynamics and risk factors;
  2. Senotherapeutic innovators looking to better understand the opportunities and challenges senotherapeutics face;
  3. Existing senotherapeutic companies looking to secure investment for future funding rounds;
  4. Investors seeking information on the different types of senotherapeutics and the strengths and weaknesses of each;
  5. Clinicians looking for an educational resource to learn about up-and-coming aspects of senotherapeutics;
  6. Executives of large pharmaceuticals to evaluate their participation in the longevity economy.

From the foreword written by our Chief Science Officer, Dr. Aubrey de Grey:

This is going to be the biggest industry ever and it’s a marketplace with 7 billion customers. Not one single person in the world is immune from aging, and these customers will be willing to spend significant amounts to stay healthy – no-one likes to be sick and no-one wants to decline. The space demands a long-term view from investment.

This thorough report from Longevity.Technology’s market intelligence unit provides important insights for the senotherapeutic market and highlights key concepts for potential investors, product developers, market entrants and academics. I hope that you find it as interesting and informative as I did and that one day we can consign aging to the history books.

PulseChain Airdrop

PulseChain Airdrop NOW LIVE!

THE SACRIFICE PHASE IS LIVE

We need you to read these instructions first!

Donors have been making costly errors that we cannot fix – please follow these instructions and make sure your donation reaches SRF.

*If you are having difficulty emailing us at [email protected], please email us at [email protected].

Please do not make your donation until you have read ALL of the instructions below and sent all of the required information. To make this easy, you can click HERE for a form to fill out with the required information – but it is critical that you first read the instructions below.

You can donate to SRF in any currency, including any cryptocurrency that is traded at Coinbase (note that, in particular, this means we cannot accept HEX or XRP). Check our DONATE page for all the methods of donation that we accept: We can only verify crypto donations sent to our wallet addresses listed on our webpage. There is no minimum donation threshold that must be met.

If it’s a crypto currency, it will have to be a coin that we accept – any coin that Coinbase trades – and our addresses are listed on our donation page cited above. To verify that your donation is yours, we are asking that you either send a source address (if it’s a non-custodial wallet), or we’ll give you a random number that your crypto donation must end in (if your wallet is on an exchange). You can also send an email to [email protected] just prior to making the donation to add an additional layer of confirmation.* WE NEED THIS INFORMATION BEFORE YOU MAKE YOUR DONATION.

You may want to send an email to [email protected] right after you make your donation – this isn’t required but will speed up how fast we can confirm your donation.*

Once your donation is processed, we’ll send you a confirmation email that will include your date of donation, its USD value, and your provided ETH wallet address within 48 hours of your donation. If this is correct, you have no further actions to take. If it is incorrect, you have 24 hours to correct any errors. After that, we will send that exact information to Richard Heart to finalize your entry into the Airdrop. Don’t worry, the actual date of your donation is the date that will be sent to Richard Heart, regardless of when we get the information to him.

Please be aware that the address you send for receipt of reward MUST have a private key associated with the address – i.e. exchanges will not work for acquiring the donation reward, it must be a decentralized or non-custodial wallet. To be clear, DO NOT SEND US YOUR PRIVATE KEY. You simply must have one on your wallet to be able to claim your reward.If you are donating in a fiat currency, we can give you our bank information or you can send a check to our address in Mountain View or use a credit card with Paypal ([email protected]). We also accept stock donations into our TD Ameritrade Account.

If you are a UK citizen and would like a tax benefit, please reach out to [email protected] to arrange your donation with SENS Foundation Europe (SENS EU). They can accept crypto and fiat donations. You’ll need to send your donation receipt from SENS EU and ETH wallet address to [email protected] to enroll in the Airdrop.*

If you are a Canadian Citizen and would like a tax benefit, please fill out and follow the instructions on this form to make a donation to Aging Research Network (ARN), a Canadian Charity aligned with SENS Research Foundation that Richard Heart has agreed to accept receipts from for the Pulse Airdrop. After you make your donation and receive your receipt from ARN, forward that receipt and your ether wallet address to [email protected], and fill out this 2nd form so that your donation information can then be forwarded to Richard Heart’s organization for processing.

Their representative Kevin will be in touch shortly. Be aware that Aging Research Network can only accept fiat donations.

Any donation we cannot verify will not be entered into the Airdrop, so please fill out this form carefully.

Any further details you need regarding the reward phase of the Airdrop, please direct to Richard Heart’s team as we are not involved with that phase.

Thank you for your support! Donors like Richard Heart, and yourself, keep SRF doing the important work to treat and cure diseases of aging. We are immensely grateful.

Live long. Live healthy.

What is the Pulse Chain Airdrop?
Cryptocurrency HEX founder Richard Heart is creating a new currency, Pulse. Prior to the launch of this new cryptocurrency, Richard is doing an Airdrop – giving away some Pulse.

How is SRF involved?
Richard is a long-time supporter of SRF and is asking that people “sacrifice”, or make a donation, to SRF during the sacrifice phase. Making a donation to SRF will enter you into the Airdrop and a chance to earn Pulse when it launches, free of charge. Note that you should NOT make the donation until we notify you that the sacrifice phase has begun, but you should notify us of your intent to donate (see below).

Does the donation have to be in cryptocurrency?
No! That’s the best part. You can donate ANY currency: crypto, credit, stock, fiat. We will liquidate it for its USD value and communicate that donation value to Richard along with the Ethereum wallet address you provide to us.

Is this donation still tax deductible?
SRF is a 501(c)(3) non-profit in the United States, so any donation made to SRF should be tax deductible in America and you will receive a tax receipt for your donation – but please consult with your tax advisor. If you are in the UK, Canada, or some countries in mainland Europe, your donation can also be tax deductible. Please see below for further instructions.

Still interested?
Below are the guidelines for participating in the Airdrop. Please make sure you read through all of the instructions prior to participation.

General Rules

Prior to donation, please send your Ethereum wallet address to [email protected] along with any details you can share regarding your donation. If you have already done this, you are all set! No need to send another email.

You may want to tell us:

  • What currency you are donating in
  • How much of that currency
  • When you will be sending the donation
  • Your full name (optional, but possibly required for a donation receipt – check with your tax advisor)
  • Any of the verification information required below

You can donate to SRF in any currency. Check the Donate page for the methods of donation that we accept. There is no minimum donation threshold that must be met. Every dollar counts.

If you are donating a cryptocurrency, it will have to be a coin that we accept – any coin that Coinbase trades – and our addresses are listed on our donation page cited above.

For verification purposes:

  • If the wallet that is SENDING crypto is decentralized (such as a MetaMask or Trust wallet) and therefore NOT on an exchange, please send the wallet address.
  • If the wallet that is SENDING crypto IS on an exchange (such as Coinbase or Binance) we must give you a random number that your crypto donation must contain as you will not be able to send a source address.

The Ethereum wallet address you send for receipt of reward must have a private key – i.e. exchanges will not work for acquiring the donation reward. To be clear, do NOT send us your private key. You simply must have one on your wallet to be able to claim your reward.

Richard Heart suggests MetaMask – which is a phone-friendly and easy to use decentralized crypto wallet.

If you are donating in a fiat currency, we can give you bank information, or you can:

  • use a credit card with Paypal,
  • send stock or bonds to our TD Ameritrade account, or
  • mail a check to our Research Center at the address below:

SENS Research Foundation, Inc.
ATTN: Airdrop
110 Pioneer Way, Ste. J
Mountain View, CA 94041
USA

At the end of the Sacrifice phase, you will receive a notice via email confirming:

  • your donation,
  • the USD value that it was liquidated at, and
  • the ETH address to be sent to Richard Heart.

If this information is correct, please do not respond to the notice. If it is incorrect, please contact [email protected] to correct the information.

It is important to note that Richard Heart has requested that the USD value of your donation be listed at the value it was liquidated, not received. We guarantee liquidation of all non-fiat donations within 12 hours of receipt, however we will strive for within an hour of receipt. Please note that prices of cryptocurrencies vary widely and we will do our best (for you and for us) to liquidate your donation as quickly as possible to minimize any value discrepancy.

Tax Considerations

United States Citizens:
SRF can provide a donation receipt to any donor. All donors will receive a donation receipt for tax purposes, however you may want to include your full name so that we can include that on your donation receipt. Please note that only US tax payers can use this donation receipt for their taxes. The donation value for tax purposes is the USD value of donation at the time of donation.


United Kingdom Citizens:
SENS Foundation Europe is a registered charity in the UK and is accepting donations for the Airdrop initiative. They accept bank transfers, wires, checks, and cryptocurrencies. Email our Airdrop address if you need further information.


European Citizens:
SENS Foundation Europe partners with Transnational Giving Europe (TGE) to provide tax benefits to European citizens in their country of residence. Please go to this link to see if there is an affiliated charity in your country. You will need to contact the charity in your country to see what donations they accept and to direct your donation to SENS Foundation Europe. Please email if you have any issues.


Canadian Citizens:
Tax-deductible receipts for donations made to the Canadian Charity, Aging Research Network (http://www.agenet.org) (ARN) will be accepted for the Airdrop Initiative. Please contact us for more information on donating to ARN. This will provide Canadian citizens with a tax benefit, but can only accept fiat currency at this time. Please email for further information and instructions.

Lipofuscin Degradation by Bacterial Hydrolases

German Institute of Human Nutrition

Principal Investigator: Tilman Grune
Research Team: Annett Braune, Annika Höhn, Tim Baldesperger

Prof. Grune is the Scientific Director of the German Institute of Human Nutrition and has been working on protein degradation of damaged proteins and aging.

Lipofuscin (LF) is a strongly oxidized material composed of covalently cross-linked proteins, lipids, and carbohydrates. Cellular LF increases with age and negatively correlates with the remaining life span of cells. Lipofuscin accumulation is especially pronounced in postmitotic cells (including cardiomyocytes and neurons) as these cells are unable to “dilute” their lipofuscin via cell division. LF by itself impairs cardiomyocyte function by declining its contractility. Importantly, no known mammalian enzyme degrades lipofuscin, therefore LF accumulates within the cell, mostly within the lysosomes.

Microorganisms, particularly bacteria, possess a wide array of enzymes that allow the degradation of any conceivable molecule formed in nature. The project, therefore, aims at identifying bacterial enzymes able to degrade LF. The project includes the following tasks:

  • isolation of human LF and identification of its components,
  • identification of microbial hydrolases able to degrade LF, and
  • testing the effect of identified hydrolases and their products in living cardiomyocytes.

Research Highlights:

Prof. Grune has previously studied the role of lipofuscin in proteasomal inhibition in human cell culture models using artificial lipofuscin. Later, he worked with isolated lipofuscin from human retinal epithelial cells and described the effects of this material on microglial cells. After securing a reliable source of human hearts, the Grune team began isolating real tissue lipofuscin. They are presently working to analyze composition and quantify degradation of LF.  In recent years, the team has also worked with “artificial” lipofuscin and shown in a preliminary experiment that degradation by bacterial enzymes is possible. Upgrades to primary human material will allow optimization of the process of identifying bacterial enzymes with the ability to degrade the material.

Catalyzing Degradation of Tau Aggregates

  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding
  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding

Tau is the major microtubule-associated protein (MAP) in mature neurons in the central nervous system. The MAPT (microtubule-associated protein tau) gene encodes for six splice variants that are highly soluble; their main function is interacting and stabilizing microtubules, along with other MAPs. The ability of tau to stabilize the microtubule is aided by its phosphorylation.

Hyperphosphorylation of tau depresses its biological activity and can lead to destabilization of microtubules. Also, hyperphosphorylation of tau proteins can cause it to aggregate into oligomers, which in turn assemble into helical and straight insoluble filaments and ultimately mature into neurofibrillary tangles (NFTs).

In Alzheimer’s disease brain, tau is three to four-fold more hyperphosphorylated than in the normal adult brain, leading to a pathological buildup of NFTs. The accumulation of NFTs comprising hyperphosphorylated tau is also observed in normal aging (PMID: 24548606).

Various other neurodegenerative diseases, collectively called tauopathies – including Pick’s disease, corticobasal degeneration, progressive supranuclear palsy, frontotemporal lobar dementia with Parkinsonism linked to chromosome 17 (FTDP-17), and dementia pugilistica – are also caused by tau aggregation.

In consultation with SRF-supported biotech company Covalent Bioscience, SENS Research Foundation has initiated a project to develop a novel way to remove abnormally aggregated tau as a therapeutic intervention with potential relevance to mitigating normal age-dependent cognitive decline, as well as for tauopathies like Alzheimer’s disease and related dementias.

Covalent Bioscience have previously demonstrated the therapeutic potential of catabodies in a recent publication targeting Transthyretin (TTR) that forms misfolded b-sheet aggregates responsible for age-associated amyloidosis. In this paper they have described catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR) (PMID: 24648510).

Team Members

We’re Hiring!

Please visit the Work With Us page to learn about available positions.

Principal Investigator

Dr. Amit Sharma

Dr. Amit Sharma

Dr. Amit Sharma was awarded a Master’s degree in Biomedical Sciences from Delhi University, India.  He received his PhD in 2009 in Biotechnology from University of Pune for his work demonstrating microRNA regulation of cytokines involved in allergic inflammation in mice model. Dr. Sharma’s postdoctoral research at the Buck Institute, Novato California involved investigating novel molecular regulatory pathways involved in genotoxic stress and cellular senescence in invertebrate and mammalian models.

Dr. Sharma has recently joined SENS Research Foundation as Group Lead in the Senescence Immunology Research Group. His research focus involves studying how aging and senescence affects the immune system and his research group will also investigate strategies to harness the immune system in mitigating deleterious effects of senescent cells with translational focus.

Publications

Previous Publications by Dr. Sharma

Sharma A, Kumar M, Aich J, Hariharan M, Brahmachari S.K, Agrawal A and Ghosh B. Post-Transcriptional Regulation of Interleukin-10 Expression by hsa-miR-106a. Proc Natl Acad Sci U S A. 2009; 106: 5761-6. PMC 2659714

Sharma A, Kumar M, Ahmad T, Mabalirajan U, Aich J, Agrawal A and Ghosh B. Antagonism of mmu- mir-106a attenuates asthma features in allergic murine model. JAP, 2012.

Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, Ghosh B. Let-7 microRNA- mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol. 2011. PMID 21616524 

Kumar S, Sharma A and Madan B, Singhal V and Ghosh B. Isoliquiritigenin inhibits IkappaB kinase activity 
and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human 
endothelial cells. Biochem Pharmacol. 2007; 73:1602-12. 


Tanveer A, Mabalirajan U, Sharma A, Ghosh B, Agrawal A. Simvastatin Improves Epithelial Dysfunction 
and Airway Hyperresponsiveness: From ADMA to Asthma. Am J Respir Cell Mol Biol. 2011 Apr;44 (4):531- 
9. PMID 2055877

Ghosh B, Kumar S, Balwani S, Sharma A. Cell adhesion molecules: therapeutic targets for developing 
novel anti-inflammatory drugs. Advanced Biotech. 2005; 4:13-20. 


Sharma S, Sharma A, Kumar S, Sharma S.K. and Ghosh B. Association of TNF haplotypes with Asthma, 
Serum IgE levels and correlation with serum TNF-α levels. Am J Respir Cell Mol Biol. 2006; 35: 488-95.

Sharma A, Joseph Wu. MicroRNA Expression Profiling of Human Induced Pluripotent and Embryonic Stem Cells. Methods in molecular biology, a part in Springer Science. PMC 3638037

Sharma A, Diecke S, Zhang WY, Lan F, He C, Mordwinkin NM, Chua KF, Wu JC. The role of SIRT6 protein in aging and reprogramming of human induced pluripotent stem cells. J Biol Chem. 2013. PMID 23653361.

Lang S, Bose N, Wilson K, Brackman D, Hilsabeck T, Watson M, Beck J, Sharma A, Chen L, Killlilea D, Ho S, Kahn A, Giacomini K, Stoller M, Chi T, Kapahi P. A conserved role of the insulin-like signaling pathway in uric acid pathologies revealed in Drosophila melanogaster. bioRxiv 387779

Akagi K, Wilson K, Katewa SD, Ortega M, Simmons J, Kapuria S, Sharma A, Jasper H, Kapahi P. Dietary restriction improves intestinal cellular fitness to enhance gut barrier function and lifespan in D. melanogaster. PloS Genet. 2018 Nov 1; 14(11):e1007777. PMC6233930.

Sharma A, Akagi K, Pattavina B, Wilson KA, Nelson C, Watson M, Maksoud E, Ortega M, Brem R, Kapahi P. Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal homeostasis and survival in Drosophila. Sci Reports. 2020 Nov 5;10(1):19080.

Full list of published work as found in My Bibliography:

https://www.ncbi.nlm.nih.gov/sites/myncbi/amit.sharma.2/bibliography/55316754/public/?sort=date&direction=ascending

Photos

Resources

Funding

To support our work please consider making a donation to SENS Research Foundation!

Thanks to our existing funders:

Engineering New Mitochondrial Genes to Restore Mitochondrial Function (MitoSENS)

  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding
  • Research Info
  • Team Members
  • Publications
  • Photos
  • Funding

Mitochondria perform and support several vital functions in a cell, and the alternate genome, mtDNA, plays a critical role in organelle maintenance. There is increasing evidence that mitochondrial function declines with age, and that dysfunctional mitochondria adversely contribute to several metabolic and neuromuscular diseases. Our goal is to address age-acquired and inborn errors of mutation in the mtDNA using a gene therapy approach. We are exploring:

  1. allotopic expression (expressing mtDNA genes from the nucleus), and
  2. whole-organelle replacement

as strategies to revitalize mitochondrial function. Our multidisciplinary approach employs cell culture and mouse models to achieve our objectives.

Allotopic Expression of Proteins Encoded in the Mitochondrial DNA

Mitochondria are the ‘power plants’ in every mammalian cell responsible for the efficient conversion of nutrients to energy. Impaired mitochondrial function and mutations in mtDNA contribute to several age-related illnesses, including Alzheimer’s Disease, Parkinson’s disease, and sarcopenia. Point mutations in any of the 13 protein-coding regions, as well as micro- and macro- deletions in the mtDNA, lead to several monogenic and organelle-specific diseases (MELAS, MEERF, LHON, Leigh’s disease to name a few). However, alterations in the OriH / OriL regions in the mtDNA can lead to global impairment in the transcription and translation of the mitochondrial genome. The mitochondrial proteome, however, consists of ~1400 proteins of which all except for the 13 polypeptides translated on the mitochondrial genome originate from the host’ nucleus. Over the course of evolution, mitochondria have developed sophisticated mechanisms to import these nuclear mitochondrial proteins. These mechanisms employ intricate translocases and signals, which are directed to different regions within the organelle.

The goal of this project is to determine how we might achieve optimal parameters for coding and non-coding regions to efficiently express and target the 13 mtDNA genes to the respiratory chain from the nucleus. Toward this end, we employ molecular biology, biochemistry and computational strategies, and refine and build on our existing knowledge of import conditions for the numerous nuclear mitochondrial proteins already delineated. We use patient-derived cybrids and animal models in assessing the functional utility of our constructs. Ultimately, we aim to express the mtDNA genes individually or in combination to overcome age-related changes to the mtDNA and improve overall organelle fitness. Please see here for recent progress on this project.

Reversing Age-Induced Mitochondrial Damage through Organelle Transplantation

Intercellular mitochondria exchange occurs naturally in the human body between cell types, typically between healthy and damaged cells. Three different transfer mechanisms have been observed:

  1. stem cells release naked mitochondria that are taken up by other cells,
  2. mitochondria are released extracellularly, enclosed in vesicles that are in turn taken up by recipient cells (possibly via endocytosis), or
  3. mitochondria migrate from one cell to another through specialized structures in vivo, such as nanotubes.

The goal of this project is to evaluate the potential of mitochondrial transfer to counteract age-related loss of tissue function. We aim to develop strategies to purify viable mitochondria and deliver them to target regions in the body.

Team Members

We’re Hiring!

Please visit the Work With Us page to learn about available positions.

Principal Investigator

amutha-boominathan

Amutha Boominathan, PhD

Research Staff

BhavnaDixit-1a-o

Bhavna Dixit, MS (Research Associate II)

begelman

David Begelman, BS (Research Associate I)

Carly Truong_headshot

Carly Truong, BS (Research Technician)

Postbaccalaureate Fellows

Summer Scholars

Placeholder-Person-1

Jay-Miguel Fonticella (Class of 2022, Tufts University, BS)

Emily Wallace_headshot

Emily Wallace (Class of 2024, U Mich. BSE)

Lab Alumni

Research Staff

  • Jayanthi Vengalam (2012-2015) – now at Protagonist Therapeutics
  • Shon Vanhoozer (2014-2017)
  • Kathleen Powers (2015-2017) – now at Bristol Myers Squibb
  • Caitlin Lewis (2017-2021) – now at SENS Research Foundation CSO Team

Summer Scholars and Postbaccalaureate Fellows

Publications

Photos

Resources

Funding

To support our work please consider making a donation to SENS Research Foundation!

Thanks to our existing funders:

The Foster Foundation

Enhancing Innate Immune Surveillance of Senescent Cells

  • Research Info
  • Team Members
  • Publications
  • Resources
  • Photos
  • Funding
  • Research Info
  • Team Members
  • Publications
  • Resources
  • Photos
  • Funding

When normal cells lose their ability to replicate, they become senescent cells. Over time, senescent cells accumulate in aging tissues, spewing off a cocktail of inflammatory and growth factors, as well as enzymes that break down surrounding tissue and cause inflammation. This phenomenon is known as the “senescence-associated secretory phenotype” (SASP). Senescent cells – and the downstream impact of the SASP – are now implicated in a remarkable litany of the diseases of aging.

On a more encouraging note, multiple studies have now documented that “senolytic” drugs and gene therapies that destroy senescent cells exert sweeping rejuvenating effects in aging, both in laboratory animals and animal models of multiple diseases of aging. In theory, however, senolytic therapies shouldn’t be necessary. The body’s immune system is on continuous patrol against senescent cells: our natural killer (NK) cells recognize senescent cells as abnormal, bind to them, and release substances that trigger the senescent cells to self-destruct.

An SRF-donor-funded collaboration between Dr. Judith Campisi’s lab at the Buck Institute and the SRF Research Center seeks to discover why senescent cells accumulate with age, and what might we do to enhance immune surveillance and elimination of these cellular saboteurs?

Research Highlights:

The Campisi lab has recently published three papers describing the underlying mechanism of immune evasion by resistant senescent cells (Pereira et al., 2019, Munoz et al., 2019, and Kale et al., 2020). Dr. Campisi has found that a significant proportion of senescent cells manage to evade destruction, even by fresh NK cells. These ‘resistant’ cells escape immunosurveillance and accumulate in aging tissues. Senescent cells moreover shed decoy ligands binding to NK cell receptors; another aim of this work is to screen for more such ligands shed by senescent cells.

The Buck-SRF-RC collaboration is now seeking to drill further into the mechanism of senescent cell accumulation, and test interventions. At the SRF-RC, we are currently perfecting the method of co-culturing NK and senescent cells and controlling the killing process;  next, we will begin testing therapeutic interventions.

The SRF-RC scientists are also working for the first time with NK cells derived directly from aged human donors (rather than long-cultured lines of NK cells, or NK cells artificially “aged” by exposure to oxidative stress or extensive replication in culture, as has been done in the past). Using these cells will allow them to observe any direct effects of aging on NK cell senolytic activity.

Goals:

The primary goal of the laboratory is to find ways to avoid the accumulation with a focus on the immune system:

  • Reversing diminished immune surveillance
  • Use of NK cells to remove senescent cells

Goal 1: Natural killer cells are primary drivers of immune surveillance of senescent cells. This project involves isolation and characterization of age-dependent changes in the phenotypes of Natural Killer cells. This is to investigate if the age of subjects effects the ability of NK cells to eliminate senescent cells in vitro and in vivo.

Goal 2: We have identified several unique antigens expressed on the surface of senescent cells. The goal of this project is the targeted elimination of senescent cells by CAR-NK therapy. We are characterizing the surface an antigen on senescent cells and investigate if targeting this antigen can enhance NK cell-mediated clearance of senescent cells from patient-derived primary endothelial cells and fetal lung fibroblasts. The ultimate goal of the project is to demonstrate that the CAR-NK cells that are capable of eliminating senescent cells in ex vivo and mouse models.

Goal 3: Senescent cells are known to secrete a unique mixture of proinflammatory cytokines, chemokines and matrix modifying proteins called the SASP (Senescence Associated Secretory Phenotype). We have identified several SASP factors that may block immune surveillance by NK cells. Proof of principle experiments are currently being performed to investigate if selective removal of specific SASP factors can enhance immune surveillance of senescent cells. The long-term goal of this project is to develop therapeutic interventions based on removal of these SASP proteins for aging and related diseases.

Team Members

We’re Hiring!

Please visit the Work With Us page to learn about available positions.

Principal Investigator

Dr. Amit Sharma

Dr. Amit Sharma

Dr. Amit Sharma was awarded a Master’s degree in Biomedical Sciences from Delhi University, India.  He received his PhD in 2009 in Biotechnology from University of Pune for his work demonstrating microRNA regulation of cytokines involved in allergic inflammation in mice model. Dr. Sharma’s postdoctoral research at the Buck Institute, Novato California involved investigating novel molecular regulatory pathways involved in genotoxic stress and cellular senescence in invertebrate and mammalian models.

Dr. Sharma has recently joined SENS Research Foundation as Group Lead in the Senescence Immunology Research Group. His research focus involves studying how aging and senescence affects the immune system and his research group will also investigate strategies to harness the immune system in mitigating deleterious effects of senescent cells with translational focus.

Postdoctoral Fellow

Research Associate

Kristie_web

Kristie Kim
Identification and characterization of the surfaceome of senescent cells and development of CAR-NK cells to enhance immune surveillance

Postbaccalaureate Fellow

Gina Zhu (Postbaccalaureate Fellow, 2020-2021)
Identifying Novel Mechanisms to Enhance Natural Killer Cell Mediated Surveillance and Clearance of Senescent Cells

Summer Scholar

Chloe Amber Lindberg (Summer Scholar, 2021)
Investigating the effect of senescence-associated secretory phenotype (SASP) factors on NK cell function

Lab Alumni

Elena Fulton (Postbaccalaureate Fellow, 2019-2020)
Characterization of age dependent changes in peripheral NK cell phenotypes in humans

Mikayla Stabile (Summer Scholar, 2020)
Characterization of age dependent changes in peripheral NK cell phenotypes in humans

Publications

  • Kale A, Sharma A, Stolzing A, Desprez PY, Campisi J. Role of immune cells in the removal of deleterious senescent cells. Immun Ageing 2020 Jun 3;17:16. PubMed: 32518575.

Previous Publications by Dr. Sharma

Sharma A, Kumar M, Aich J, Hariharan M, Brahmachari S.K, Agrawal A and Ghosh B. Post-Transcriptional Regulation of Interleukin-10 Expression by hsa-miR-106a. Proc Natl Acad Sci U S A. 2009; 106: 5761-6. PMC 2659714

Sharma A, Kumar M, Ahmad T, Mabalirajan U, Aich J, Agrawal A and Ghosh B. Antagonism of mmu- mir-106a attenuates asthma features in allergic murine model. JAP, 2012.

Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, Ghosh B. Let-7 microRNA- mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol. 2011. PMID 21616524 

Kumar S, Sharma A and Madan B, Singhal V and Ghosh B. Isoliquiritigenin inhibits IkappaB kinase activity 
and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human 
endothelial cells. Biochem Pharmacol. 2007; 73:1602-12. 


Tanveer A, Mabalirajan U, Sharma A, Ghosh B, Agrawal A. Simvastatin Improves Epithelial Dysfunction 
and Airway Hyperresponsiveness: From ADMA to Asthma. Am J Respir Cell Mol Biol. 2011 Apr;44 (4):531- 
9. PMID 2055877

Ghosh B, Kumar S, Balwani S, Sharma A. Cell adhesion molecules: therapeutic targets for developing 
novel anti-inflammatory drugs. Advanced Biotech. 2005; 4:13-20. 


Sharma S, Sharma A, Kumar S, Sharma S.K. and Ghosh B. Association of TNF haplotypes with Asthma, 
Serum IgE levels and correlation with serum TNF-α levels. Am J Respir Cell Mol Biol. 2006; 35: 488-95.

Sharma A, Joseph Wu. MicroRNA Expression Profiling of Human Induced Pluripotent and Embryonic Stem Cells. Methods in molecular biology, a part in Springer Science. PMC 3638037

Sharma A, Diecke S, Zhang WY, Lan F, He C, Mordwinkin NM, Chua KF, Wu JC. The role of SIRT6 protein in aging and reprogramming of human induced pluripotent stem cells. J Biol Chem. 2013. PMID 23653361.

Lang S, Bose N, Wilson K, Brackman D, Hilsabeck T, Watson M, Beck J, Sharma A, Chen L, Killlilea D, Ho S, Kahn A, Giacomini K, Stoller M, Chi T, Kapahi P. A conserved role of the insulin-like signaling pathway in uric acid pathologies revealed in Drosophila melanogaster. bioRxiv 387779

Akagi K, Wilson K, Katewa SD, Ortega M, Simmons J, Kapuria S, Sharma A, Jasper H, Kapahi P. Dietary restriction improves intestinal cellular fitness to enhance gut barrier function and lifespan in D. melanogaster. PloS Genet. 2018 Nov 1; 14(11):e1007777. PMC6233930.

Sharma A, Akagi K, Pattavina B, Wilson KA, Nelson C, Watson M, Maksoud E, Ortega M, Brem R, Kapahi P. Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal homeostasis and survival in Drosophila. Sci Reports. 2020 Nov 5;10(1):19080.

Full list of published work as found in My Bibliography:

https://www.ncbi.nlm.nih.gov/sites/myncbi/amit.sharma.2/bibliography/55316754/public/?sort=date&direction=ascending

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Funding

To support our work please consider making a donation to SENS Research Foundation!

Thanks to our existing funders:

Job Opportunity: Research Associate / Scientist – Boominathan Lab (MitoSENS)

Job Type: Full-time
Number of Positions: 2
Title: Research Associate/Scientist – Boominathan Lab
Salary: Pay is salaried, commensurate with experience and local rates; typically from $55,000/year.

Qualifications:

  • Bachelor’s/Masters/PhD
  • Laboratory experience: 2 years (Preferred)

The Boominathan lab at SENS Research Foundation (www.sens.org) is hiring highly motivated Research Scientists / Associates for a project geared toward translational therapies for mitochondrial dysfunctions. SENS Research Foundation is located in the heart of Silicon Valley (Mountain View, CA) and is close to several premier research organizations and major biotech hubs. Ours is an exciting, cutting-edge non-profit organization dedicated to transforming the way the world treats aging. More detailed information can be found at http://sens.org/research/intramural/allotopic-expression.

The successful candidate will use in vitro, in vivo and stem cell models to address diseases due to mtDNA mutations. This research position is within a small but dynamic group that strives to develop a deep understanding and curative therapies using a gene therapy approach to treat mitochondrial myopathies. Qualified candidates will have a BS/MS in the biological sciences and at least 2 years of relevant work experience. Recent PhDs with an exposure to mitochondria biology will be considered for a Research Scientist position. Duties will include performing wet lab experiments, recording, and analyzing data, and presenting the results in formal meetings every 2-3 months.

The ideal applicant will have experience in tissue culture, microscopy, flow cytometry and molecular biology with an exposure to protein analysis and biochemical assays. Hands on experience working with rodents is highly desirable. Experience working with mitochondria or interest in protein modelling are a big plus, but not required.

Other qualities:

  • Problem-solving
  • Team player
  • Creativity and the ability to think beyond an experiment to envision the path to success
  • Capacity to adapt as priorities and requirements change
  • Ability to plan and document your work diligently
  • Excellent written and verbal communication skills in English
  • Positive spirit, a real drive for science

We offer an excellent benefits package including paid vacation and sick leave, fully covered health and dental insurance (inclusive of dependents), an FSA program, and a company-matched 401(k) plan, all of which is offered after a 90-day introductory period. SENS Research Foundation is an equal opportunity employer. We may sponsor a visa for international applicants.

The positions are available now and will be filled as soon as qualified candidates are found. Salary is commensurate with job experience.

TO APPLY:

Interested candidates should apply by emailing a cover letter stating their scientific interests and current CV to [email protected].

COVID-19 considerations:

All employees are to follow COVID restrictions, which will lighten as our workplace is vaccinated. All employees are expected to wear PPE. Vaccinating is strongly encouraged.

Job Opportunity: Postdoctoral Research Fellow – Catabody Project

Job Type: Full-time
Title: Postdoctoral Research Fellow – Catabody Project
Salary: Pay is salaried, commensurate with experience and local rates; typically around $60,000/year.

Qualifications:

  • Doctorate (Preferred)
  • Molecular biology: 2 years (Preferred)
  • Wet chemistry: 2 years (Preferred)

SENS Research Foundation (SRF) is hiring a postdoctoral research fellow for our Research Center (RC) located in Mountain View, CA. SRF is an exciting, cutting-edge non-profit dedicated to transforming the way the world researches and treats aging.

More detailed information can be found here.

We seek a postdoctoral fellow to join our small but dynamic immunology team led by Dr. Amit Sharma. The project geared towards developing a novel way to remove abnormal tau aggregation. The project is potentially relevant for developing therapeutic mitigation of normal age-dependent cognitive decline, as well as for tauopathies like Alzheimer’s Disease and Related Disorders. This project involves utilizing enzymatic antibodies to target toxic tau aggregates. As part of the project we will explore ways of delivering antibodies into cells. We will use human iPS derived neuronal cells as a model system to test the catalytic antibodies and confirm tau degradation. The project involves extensive use of cell culture and mice models and involves working with human blood samples, primary human cells, and mice tissue. Duties will include performing wet-lab experiments, recording and analyzing data, and presenting the results in meetings every 2-3 months.

Experience:

  • Ph.D. in chemical/biological sciences and substantial bench experience or several years of industry experience
  • immunology
  • antibody design/production/screening
  • general molecular biology techniques (such as quantitative real-time PCR, Western blot, immunofluorescence, ELISA.)
  • iPSC culturing and neuronal differentiation

Other qualities:

  • Problem-solving
  • Team player
  • Creativity and the ability to think beyond an experiment to envision the path to success
  • Capacity to adapt as priorities and requirements change
  • Ability to plan and document your work diligently
  • Excellent written and verbal communication skills in English
  • Positive spirit, a real drive for science

We offer an excellent benefits package including paid vacation and sick leave, fully covered health and dental insurance (inclusive of dependents), an FSA program, and a company-matched 401(k) plan, all of which is offered after a 90-day introductory period. SENS Research Foundation is an equal opportunity employer. The job offer comes with two years contract with the possibility of an extension. We may sponsor a visa for international applicants.

The position is available now and will be filled as soon as the qualified candidate is found. Salary is commensurate with the job title.

TO APPLY:

Interested candidates should apply by emailing a cover letter and current CV to [email protected].

COVID-19 considerations:

All employees are to follow COVID restrictions, which will lighten as our workplace is vaccinated. All employees are expected to wear PPE. Vaccinating is strongly encouraged.

Job Opportunity: Research Associate – Catabody Project

Job Type: Full-time
Title: Research Associate
Salary: Pay is salaried, commensurate with experience and local rates; typically around $55,000/year.

Qualifications:

  • Master’s (Preferred)
  • Laboratory experience: 1 year (Preferred)
  • Wet chemistry: 1 year (Preferred)

SENS Research Foundation (SRF) is hiring a Research Associate for our Research Center (RC) located in Mountain View, CA. SRF is an exciting, cutting-edge non-profit dedicated to transforming the way the world researches and treats age-related diseases. More detailed information can be found at our website: www.sens.org

We seek a Research Associate to join our small but dynamic immunology team led by Dr. Amit Sharma. The project geared towards developing a novel way to remove abnormal tau aggregation. The project is potentially relevant for developing therapeutic mitigation of normal age-dependent cognitive decline, as well as for tauopathies like Alzheimer’s Disease and Related Disorders. This project involves utilizing enzymatic antibodies to target toxic tau aggregates. As part of the project we will explore ways of delivering antibodies into cells. We will use human iPS derived neuronal cells as a model system to test the catalytic antibodies and confirm tau degradation. The project involves extensive use of cell culture and mice models and involves working with human blood samples, primary human cells, and mice tissue. Duties will include performing wet-lab experiments, recording and analyzing data, and presenting the results in meetings every 2-3 months.

The ideal candidate for this full-time position has a Ph.D. in chemical/biological sciences and substantial (or the master’s degree with at least 1-2 years) bench experience, industry experience position is preferred. The candidate must be adaptable, a team player, self-motivated, and interested in problem-solving. Duties will include performing wet-lab experiments, recording and analyzing data, and presenting the results in meetings every 2-3 months.

The ideal candidate must have experience with molecular biology techniques, such as quantitative real-time PCR, Western blot, immunofluorescence, ELISA, microplate readers, and flow cytometry analysis, as well as prior experience performing data analysis and presenting data. Preference will be given to candidates with experience in primary cell culture and PBMC isolation from human blood.

We offer an excellent benefits package including paid vacation and sick leave, fully covered health and dental insurance (inclusive of dependents), an FSA program, and a company-matched 401(k) plan, all of which is offered after a 90-day introductory period. SENS Research Foundation is an equal opportunity employer. The job offer comes with two years contract with the possibility of an extension. We may sponsor a visa for international applicants.

The position is available now and will be filled as soon as the qualified candidate is found. Salary is commensurate with the job title.

TO APPLY:

Interested candidates should apply by emailing a cover letter and current CV to [email protected].

COVID-19 considerations:

All employees are to follow COVID restrictions, which will lighten as our workplace is vaccinated. All employees are expected to wear PPE. Vaccinating is strongly encouraged.

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