Head of Translational Genomics

Are you ready to spearhead Gordian's efforts to improve clinical success rates by matching our targets and vast genomic datasets from different species to patient endotypes, working with disease experts to set a vision for collecting and analyzing samples to reduce uncertainty about translation to patients?

The Destination:

Gordian Biotechnology is a therapeutics company whose mission is to cure age-related diseases and ultimately allow people to lead longer, healthier lives. Traditional ex vivo screening methods have failed to produce effective treatments, as age-related diseases have complex causes that include interactions with the aged environment. To address this problem, Gordian's platform is the first and only to enable pooled in vivo tests at scale in our proprietary "Patient Avatars". We are able to deliver and test hundreds of therapeutics in individual animals, and scale efficacy testing to cover every therapeutic target at the beginning of the drug discovery process (more info on our website). We can choose targets that really impact disease biology, to develop and commercialize therapies for the world's deadliest diseases, and eventually for the processes of aging itself.

The Journey:

Our mission is audacious, and the path will be full of both challenges and excitement. Two things characterize the Gordian experience: 1) We work as a team, with ownership in our own roles and trust in each other. 2) We strive for extraordinary outcomes, and in doing so grow our skills and capability.

Team – Relying on each other begins with transparency. We set clear goals, visibly connecting individuals and teams to our company objectives. This empowers each of us to make autonomous decisions about our work, knowing how they will affect the bigger picture. Our communication happens out in the open. We give and receive feedback from a perspective of helping each other grow, share mistakes, and ask for help.

Extraordinary – Every day, we ask ourselves 'could this process/outcome be even better?'. Knowing our overall mission, we do what we think helps us make the most progress, without asking for permission. We don't shy away from big challenges or unknown territory, but find a way to excel. Our colleagues are amazing, both at what they do and as people. They inspire us to keep up, to not let them down, and be inspiring in return.

Like any cutting-edge research environment, Gordian doesn't believe in a standard 9 to 5 day. We set ambitious project goals and support each other to meet them, while maintaining the balance individuals need to thrive and achieve excellence. Our team is geared towards helping each other out and maintaining a culture of intellectual and social fun. We like getting things done and keep standing meetings to a minimum. This year, in accordance with our unlimited vacation policy, each member took an average of 4.5 weeks of (offline) vacation, not including major holidays. We unwind with weekly team lunches, and support each others' projects both experimentally and by 'pre-mortem' meetings to discuss possible failure modes and experimental design.

If this environment sounds appealing, help us bring it to life. We are at the beginning of a long journey, and want both your ability and your personality along for the ride. Our culture is a source of great pride; it represents both who we are, and who we wish to be. You can dive deeper here

About the Role:

Your primary mission as human genomics lead is to set our first clinical trials up for success by using our preclinical data to inform patient selection, suggestive biomarkers for treatment efficacy, and translatability of models. Working closely with disease program leads and our broader computational team, you will lead the development of computational analyses aimed at evaluating different approaches we can take to identify responders vs. nonresponders, including genetic segmentation, mechanism-based biomarkers, conservation of biology from preclinical models, and more. This will serve to help us distinguish the patients most likely to respond to therapies in clinical trials, increasing our chances of success of showing target efficacy.

There are many different angles we could explore, and we will rely on your vision and experience to narrow down to paths where we can achieve the most impact on our programs within the 1-2 years before we lock in clinical plans. You'll push the focused acquisition of additional human genomic samples and data to support this vision, by expanding tissue sourcing and/or setting up collaborations to access proprietary datasets to give us further confidence in our analyses. Additionally, you'll propose additional measurements for human and/or animal studies that might unlock promising approaches for patient selection or biomarkers. You'll support these analyses by designing/guiding experiments in patient-mimicking systems that generate new types of data that allow us to evaluate and improve human translatability during our preclinical work. As our voice of 'human relevance', you help keep patient translatability top of mind across our experiments and project plans.

In your first month at Gordian, you'll get up to speed with our screening/validation process, available datasets and the state of each disease program. You'll highlight undervalued data and prioritize sample/data collection plans for each of our indications. You'll guide UKBB exploration to help segmentation or Avatar-matching for at least one program.

By month three, you'll have mapped out a plan for efficacy biomarkers in trials for each of our four indications, including the big picture project planning to enable this. For two programs you will complete exploration of possible approaches, and select projects that seem most promising for improving trial odds. Finally, you've developed a checklist for evaluating screen results from a translational genomics perspective.

In six months biomarker development is progressing as planned, and you've completed one or more projects to improve either patient selection in trials or match patients with Avatars. You'll conclude the exploratory phase for the remaining 2 programs, including project prioritization to improve trial odds.

About You:

You have a history of successful execution, both in- and outside of your job description.

You want a chance to do your best work, immerse yourself and excel, alongside people who will inspire you and whom you'll be excited to spend your days with.

You truly want to play a key role in an early-stage startup: A fast-paced environment full of both uncertainty and new challenges, demanding relentless resourcefulness.

You have been part of multiple efforts to apply translational genomics to aid drug development, and seen both successes and failures.

You know many of the pitfalls associated with patient selection and translation from preclinical studies.

You have practical experience linking genomic data to physiological measurements and/or clinical data, and a confident perspective on what methods, data, and aims will be most likely to improve predictions of translatability to humans.

1. Exploring human genetics to find biological variants relevant to therapeutic development, e.g. supporting translational relevance or identifying likely responders.

2. Comparative genomics to identify conservation of biology and responses across species

3. Single cell RNAseq, ideally on samples with high variability and/or pursuing methods to segment groups of samples.

4. Biomarker identification from clinical samples.

You have experience managing time-sensitive projects, in collaboration with different specialists. You have deep expertise, and broad curiosity. You are excited to use cutting-edge technology to find the best therapeutic targets, and turn those into drugs.

Experience with our indications (MASH, osteoarthritis, heart failure, pulmonary fibrosis) is a plus, as is experience with functional genomics, specific familiarity with genetic databases (e.g. UKBB), or connections to relevant communities (hospitals, databanks, etc.) are all pluses.

The Details:

Gordian aims to provide everything you need to thrive. Beyond our community and science, you'll have enough equity to be a true stakeholder in the company, competitive salary, full health/dental/vision/life insurance, 401k with match, onsite lunch paid for 3 days a week, an onsite gym, whatever vacation you need to be at your peak, remote work flexibility, and access to world-class mentors and advisors to support your professional growth. Our building is in the heart of the biotech capital of South San Francisco.